Growth factors as active participants in carcinogenesis: A perspective

Veterinary Pathology

Volumn 47, Issue 1, 2010, Pages 77-97

  Halper, J ^a  

^a UNIVERSITY OF GEORGIA   (United States)

Author keywords

Angiogenesis; Antibodies to receptors; Cell membrane receptors; Cell proliferation; Epidermal growth factor; Fibroblast growth factor; Granulins; Growth factors; Inhibitors of tyrosine kinases; Insulin like growth factor; Platelet derived growth factor; Transforming growth factor ; Transforming growth factor ; Tumor growth and progression; Vascular endothelial growth factor

Indexed keywords

ANTINEOPLASTIC AGENT; EPIDERMAL GROWTH FACTOR; FIBROBLAST GROWTH FACTOR; GRANULIN PRECURSOR PROTEIN; GROWTH FACTOR RECEPTOR; PLATELET DERIVED GROWTH FACTOR; SIGNAL PEPTIDE; SOMATOMEDIN; TRANSFORMING GROWTH FACTOR BETA; VASCULOTROPIN A;

ANIMAL; DRUG ANTAGONISM; DRUG EFFECT; HUMAN; NEOPLASM; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; EPIDERMAL GROWTH FACTOR; FIBROBLAST GROWTH FACTORS; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; NEOPLASMS; PLATELET-DERIVED GROWTH FACTOR; RECEPTORS, GROWTH FACTOR; SIGNAL TRANSDUCTION; SOMATOMEDINS; TRANSFORMING GROWTH FACTOR BETA; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 77949700502     PISSN: 03009858     EISSN: 15442217     Source Type: Journal    
DOI: 10.1177/0300985809352981     Document Type: Article

References (278)

1. Abraham JA, Mergia A., Whang JL, Tumolo A., Friedman J., Hjerrild KA, Gospodarowicz D., Fiddes JC: Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science 233:545-548, 1986.
2. Adams GR: Invited review: autocrine/paracrine IGF-I and skeletal muscle adaptation. J Appl Physiol 93:1159-1167, 2002.
3. American Society of Health-System Pharmacists: AFHS Consumer Medication Information [update from July 1, 2008]. Bethesda, MD.
4. Amgen: Products. http://www.amgen.com/medpro/products.html. Accessed 19 October2009.
5. Andrae J., Gallini R., Betsholtz C.: Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22:1276-1312, 2008.
6. Antuofermo E., Miller MA, Pirino S., Xie J., Badve S., Mohammed SI: Spontaneous mammary intraepithelial lesions in dogs: a model of breast cancer. Cancer Epidemiol Biomarkers Prev 16:2247- 2256, 2007.
7. Aoki CA, Borchers AT, Li M., Flavell RA, Bowlus CL, Ansari AA, Gershwin ME: Transforming growth factor β (TGF-β) and autoimmunity. Autoimmun Rev 4:450-459, 2005.
8. Baba T., Hoff HB III, Nemoto H., Lee H., Orth J., Arai Y., Gerton GI: Acrogranin, an acrosomal cystein-rich glycoprotein is the precursor of the growth-modulating peptides, granulins, and epithelins, and is expressed in somatic as male germ cells. Mol Reprod Dev 34:233-243, 1993.
9. Baker M., Mackenzie IR, Pickering-Brown SM, Gass J., Rademakers R., Lindholm C., Snowden J., Adamson J., Sadovnick AD, Rollinson S., Cannon A., Dwosh E., Neary D., Melquist S., Richardson A., Dickson D., Berger Z., Eriksen J., Robinson T., Zehr C., Dickey CA, Crook R., McGowan E., Mann D., Boeve B., Feldman H., Hutton M.: Mutations in progranulin cause taunegative fronto-temporal dementia linked to chromosome 17. Nature 442:916-919, 2006.
10. Bale LK, Conovar CA: Regulation of insulin-like growth factor binding protein-3 messenger ribonucleic acid expression by insulin-like growth factor I. Endocrinology 131:608-614, 1992.
11. Bateman A., Belcourt D., Bennett H., Lazure C., Solomon S.: Granulins: a novel class of peptides from leukocytes. Biochem Biophys Res Commun 173:1161-1168, 1990.
12. Bateman A., Bennett HP: Granulins: the structure and function of an emerging family of growth factors. J Endocrinol 158:145-151, 1998.
13. Battegay EJ, Rupp J, Iruela-Arispe L, Sage EH, Pech M: PDGF-BB modulates endothelial proliferation and angiogenesis in vitro via PDGF-β receptors. J Cell Biol 125:917-928, 1994.
14. Baxter RC, Binoux MA, Clemmons DR, Conovar CA, Drop SL, Holly JM, Mohan S., Oh Y., Rosenfeld RG: Recommendations for nomenclature of the insulin-like growth factor binding protein superfamily. J Clin Endocrinol Metabol 83:3213, 1988.
15. Berger MS, Locher GW, Saurer S., Gullick WJ, Waterfield MD, Groner B., Hynes NE: Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res 48:1238-1243, 1988.
16. Bergers G., Javaherian K., Lo KM, Folkman J., Hanahan D.: Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 284:808-812, 1999.
17. Bhandari V., Giaid A., Bateman A.: The complementary deoxyribonucleic acid sequence, tissue distribution, and cellular localization of the rat granulin precursor. Endocrinology 133:2682-2689, 1993.
18. Bhandari V., Palfree RG, Bateman A.: Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains. Proc Natl Acad Sci U S A 89:1715-1719, 1992.
19. Blobe GC, Schiemann WP, Lodish HF: Role of transforming growth factor β in human disease. N Engl J Med 342:1350- 1358, 2000.
20. Borzacchiello G., Russo V., Gentile F., Roperto F., Venuti A., Nitsch L., Campo MS, Roperto S.: Bovine papillomavirus E5 oncoprotein binds to the activated form of the platelet-derived growth factor β receptor in naturally occurring bovine urinary tumours. Oncogene 25:1251-1260, 2006.
21. Bruna A., Darken RS, Rojo F., Ocaña A., Peñuelas S., Arias A., Paris R., Tortosa A., Mora J., Baselga J., Seoane J.: High TGFβ-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell 11:147-160, 2007.
22. Buck E., Eyzaquirre A., Rosenfeld-Franklin M., Thompson S., Mulvihill M., Barr S., Brown E., O'Connor M., Yao Y., Pachter J., Miglarese M., Epstein D., Iwata KK, Haley JD, Gibson NW, Ji OS: Feedback mechamisms promote cooperativity for small molecule inhibitors of epidermal and insulin-like growth factor receptors. Cancer Res 68:8322-8332, 2008.
23. Calvo A., Catena R., Noble MS, Carbott D., Gil-Bazo I., Gonzalez-Moreno O., Huh JI, Sharp R., Qiu TH, Anver MR, Merlino G., Dickson RB, Johnson MD, Green JE: Identification of VEGFregulated genes associated with increased lung metastatic potential: functional involvement of tenascin-C in tumor growth and lung metastasis. Oncogene 27:5373-5384, 2008.
24. Carmeliet P.: Mechanism of angiogenesis and arteriogenesis. Nat Med 6:389-395, 2000.
25. Carmeliet P., Jain RK: Angiogenesis in cancer and other diseases. Nature 407:249-257, 2000.
26. Carpenter G., Cohen S.: Epidermal growth factor. J Biol Chem 265:7709-7712, 1990.
27. Carroll M., Ohno-Jones S., Tamura S., Buchdunger E., Zimmermann J., Lydon NB, Gilliland DG, Druker BJ: CGP57I48, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood 90: 4947-4952, 1997.
28. Casella SJ, Smith EP, van Wyk JJ, Joseph DR, Hynes MA, Hoyt EC, Lund PK: Isolation of rat testis cDNAs encoding an insulin-like growth factor I precursor. DNA 6:325-330, 1987.
29. Caunt M., Mak J., Liang WC, Stawicki S., Pan Q., Tong RK, Kowalski J., Ho C., Reslan HB, Ross J., Berry L., Kasman I., Zlot C., Cheng Z., Le Couter J., Filvaroff EH, Plowman G., Peale F., French D., Carano R., Koch AW, Wu Y., Watts RJ, Tessier-Lavigne M., Bagri A.: Blocking neuropilin-2 function inhibits tumor cell metastasis. Cancer Cell 13:331-342, 2008.
30. Cha JY, Lambert QT, Reuther GW, Der CJ: Involvement of fibroblast growth factor receptor 2 isoform switching in mammary oncogenesis. Mol Cancer Res 6:435-444, 2008.
31. Cha JY, Maddileti S., Mitin N., Harden TK, Der CJ: Aberrant receptor internalization and enhanced FRS2-dependent signaling contributes to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform. J Biol Chem 284:6227-6240, 2009.
32. Chaffer CL, Dopheide B., Savagner, Thompson EW, Williams ED: Aberrant fibroblast growth factor receptor signaling in bladder and other cancers. Differentiation 75:831-842, 2007.
33. Cheatham B., Kahn CR: Insulin action and the insulin signalling network. Endocrine Rev 16:117-142, 1995.
34. Cheifetz S., Weatherbee JA, Tsang ML, Anderson JK, Mole JE, Lucas R., Massagué J.: The transforming growth factor-β system, a complex pattern of cross-reactive ligands and receptors. Cell 48:409-415, 1987.
35. Cheung ST, Wong SY, Leung KL, Chen X., So S., Ng IO, Fan ST: Granulin-epithelin precursor overexpression promotes growth and invasion of hepatocellular carcinoma. Clin Cancer Res 10:7629-7636, 2004.
36. Chikama T., Liu CY, Meji JTA, Hayashi Y., Wang IJ, Yang L., Nishida T., Kao WWY: Excess FGF-7 in corneal epithelium causes corneal intraepithelial neoplasia in young mice and epithelium hyperplasia in adult mice. Am J Pathol 172:638-649, 2008.
37. Childs CB, Proper JA, Tucker RF, Moses HL: Serum contains a platelet-derived transforming growth factor. Proc Natl Acad Sci U S A 79:5312-536, 1982.
38. Chowdhury S., Larkin JM, Gore ME: Recent advances in the treatment of renal cell carcinoma and the role of targeted therapies. Br J Cancer 44:2152-2161, 2008.
39. Coffey RJ, Romano M., Polk WH, Dempsey PJ: Roles for transforming growth factor-α in gastric physiology and pathophysiology. Yale J Biol Med 65:693-704, 1992.
40. Cohen P., Peehl DM, Stamey TA, Wilson KF, Clemmons DR, Rosenfeld RG: Elevated levels of insulin-like growth factor-binding protein-2 in the serum of prostate cancer patients. J Clin Endocrinol Metab 76:1031-1035, 1993.
41. Cohen S.: Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem 237:1555-1562, 1962.
42. Cohen S., Carpenter G., King L. Jr: Epidermal growth factor-receptor-protein kinase interactions: copurification of receptor and epidermal growth factor-enhanced phosphorylation activity. J Biol Chem 255:4834-4842, 1980.
43. Cohick WS, Wang B., Verma P., Boisclair YR: Insulin-like growth factor I (IGF-) and cyclic adenosine 3′,5′-monophosphate regulate IGF-binding protein-3 gene expression by transcriptional and posttranscriptional mechanisms in mammary epithelial cells. Endocrinology 141:4583-4591, 2000.
44. Crawford Y., Ferrara N.: VEGF inhibition: insights from preclinical and clinical studies. Cell Tissue Res 335:261-269, 2009.
45. Cruts M., Gijselinck I., van der Zee J., Engelborghs S., Wils H., Pirici D., Rademakers R., Vandenberghe R., Dermaut B., Martin JJ, van Duijn C., Peeters K., Sciot R., Santens P., De Pooter T., Mattheijssens M., Van den Broeck M., Cuijt I., Vennekens K., De Deyn PP, Kumar-Singh S., Van Broeckhoven C.: Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442:920-924, 2006.
46. Culouscou JM, Carlton GW, Shoyab M.: Biochemical analysis of the epithelin receptor. J Biol Chem 268:10458-10462, 1993.
47. Cunningham MP, Thomas H., Marks C., Green M., Fan Z., Modjtahedi H.: Co-tergeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR kinase inhibitor NVP-AEW541 in colorectal cancer cells. Int J Oncol 33:1107-1113, 2008.
48. Dai C., Celestino JC, Okada Y., Louis DN, Fuller GN, Holland EC: PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev 15:1913- 1925, 2001.
49. Dalal S., Berry AM, Cullinane CJ, Mangham DC, Grimer R., Lewis IJ, Johnston C., Laurence V., Burchill SA: Vascular endothelial growth factor: a therapeutic target for tumors of the Ewing's sarcoma family. Clin Cancer Res 15:2364-2378, 2005.
50. Daniel R., He Z., Carmichael KP, Halper J., Bateman A.: Cellular localization of gene expression for progranulin. J Histochem Cytochem 48:999-1009, 2000.
51. Dejonge RR, Garrigueantar L., Velluci VF, Reiss M.: Frequent inactivation of the transforming growth factor β type II receptor in small-cell lung carcinoma cells. Oncol Res 9:89-98, 1997.
52. DeLarco JE, Todaro GJ: Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A 75:4001- 4005, 1978.
53. Deming SL, Nass SJ, Dickson RB, Trock BJ: C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance. Br J Cancer 83:1688-1695, 2000.
54. de Ostrovich KK, Lambertz I., Colby JK, Tian J., Rundhaug JE, Jonhston D., Conti CJ, DiGiovanni J., Fuchs-Young R.: Paracrine overexpression of insulin-like growth factor-1 enhances mammary tumorigenesis in vivo. Am J Pathol 173:824-834, 2008.
55. Derynck R.: Transforming growth factor-α. Mol Reprod Dev 27:2-9, 1990.
56. Diaz-Cuerto L., Stein P., Jacobs A., Schultz RM, Gerton GI: Modulation of mouse preimplantation embryo development by acrogranin (epithelin/granulin precursor). Dev Biol 217:406-417, 2000.
57. Dickinson PJ, Roberts BN, Higgins RJ, Leutenegger CM, Bollen AW, Kass PH, LeCouteur RA: Expression of receptor tyrosine kinases VEGFR-1 (FLT-1), VEGFR-2 (KDR), EGFR-1, PDGFRα and c-Met in canine primary brain tumors. Vet Comp Oncol 4:132-140, 2006.
58. Dickinson PJ, Sturges BK, Higgins RJ, Roberts BN, Leutenegger CM, Bollen AW, LeCouteur RA: Vascular endothelial growth factor mRNA expression and peritumoral edema in canine primary central nervous system tumors. Vet Pathol 45:131-139, 2008.
59. Donnem T., Al-Saad S., Al-Shibli K., Andersen S., Busund LT, Bremmes RM: Prognosis impact of platelet-derived growth factors in non-small cell lung cancer tumor and stromal cells. J Thorac Oncol 3:963-970, 2008.
60. Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA, Antoniades HN: Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221:275-277, 1983.
61. Downward J., Yarden Y., Mayes, Scrace G, Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield MD: Close similarity of the epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307:521-527, 1984.
62. Druker BJ, Talpaz M., Resta DJ, Peng B., Buchdunger E., Ford JM, Lydon NB, Kantarjian H., Capdeville R., Ohno-Jones S., Sawyers CL: Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031-1037, 2001.
63. Dutra AP, Grania NV, Schmitt FC, Cassali GD: c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors. Braz J Med Biol Res 37:1673-1681, 2004.
64. Edelberg JM, Aird WC, Wu W., Rayburn H., Mamuya WS, Mercola M., Rosenberg RD: PDGF mediates cardiac microvascular communication. J Clin Invest 102:837-843, 1998.
65. Egger B., Procaccino F., Lakshmanan J., Reinshagen M., Hoffmann P., Patel A., Reuben W., Gnanakkan S., Liu L., Barajas L., Eysselein VE: Mice lacking transforming growth factor α have an increased susceptibility to dextran-sulfate colitis. Gastroenterology 113: 825-832, 1997.
66. el Atiq F., Garrouste F., Remacle-Bonnet M., Sastre B., Pommier G.: Alterations in serum levels of insulin-like growth factors and insulin-like growth-factor-binding proteins in patients with colorectal cancer. Int J Cancer 57:491-497, 1994.
67. Elice F., Jacoub J., Rickles FR, Falanga A., Rodeghiero F.: Hemostatic complication of angiogenesis inhibitors in cancer patients. Am J Hematol 83:862-870, 2008.
68. Esparís-Ogando A., Ocaña A., Rodríguez-Barrueco R., Ferreira L., Borges J., Pandiella A.: Synergic antitumoral effect of an IGF-IR inhibitor and trastuzumab on HER2-oberexpressiong breast cancer cells. Ann Oncol 19:1860-1869, 2008.
69. Ferrara N., Gerber HP, LeCouter J.: The biology of VEGF and its receptors. Nat Med 9:669-676, 2003.
70. Finch PW, Rubin JS, Miki T., Ron D., Aaronson SA: Human KGF is FGF-related with properties of a paracrine effector of epithelial cell proliferation. Science 1989 245:752-755, 1989.
71. Fleming TP, Saxena A., Clark WC, Robertson JT, Oldfield EH, Aaronson SA, Ali IU: Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors. Cancer Res 52:4550- 4553, 1992.
72. Flint AF, U'Ren L., Legare ME, Withrow SJ, Dernell W., Hanneman WH: Overexpression of the erbB-2 proto-oncogene in canine osteosarcoma cell lines and tumors. Vet Pathol 41:291-296, 2004.
73. Folkman J.: Angiogenesis inhibitors. Cancer Biol Ther 2:S127-S133, 2003.
74. Folkman J.: Antiangiogenic activity of a matrix protein. Cancer Biol Ther 2:53-54, 2003.
75. Franzén P., ten Dijke P., Ichijo H., Yamashita H., Schultz P., Heldin CH: Cloning of a TGFβ type I receptor that forms a heteromeric complex with the TGFβ type receptor. Cell 75:681-692, 1993.
76. Fredrickson L., Li H., Erikson U.: The PDGF family: four gene products form five dimeric structures. Cytokine Growth Factor Rev 15:197-204, 2004.
77. Gama A., Alves A., Schmitt F.: Identification of molecular phenotypes in canine mammary carcinomas with clinical implications: application of the human classification. Virchows Arch 453:123- 132, 2008.
78. García-Echeverría C., Pearson MA, Marti A., Meyer T., Mestan J., Zimmermann J., Gao J., Brueggen J., Capraro HG, Cozens R., Evans DB, Fabbro D., Furet P., Porta DG, Liebetanz J., Martiny-Baron G., Ruetz S., Hofmann F.: In vivo antitumor activity of NVP-AEW541: a novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell 5:231-239, 2004.
79. Gautschi OP, Frey SP, Zellweger R.: Bone morphogenetic proteins in clinical applications. ANZ J Surg 77:626-631, 2007.
80. Genentech: Product Information. http://www.gene.com/gene/products/information/ Accessed 19 October2009.
81. Gentry LE, Webb NR, Lim GJ, Brunner AM, Ranchalis JE, Twardzik DE, Lioubin MN, Marquardt H., Purchio AF: Type 1 transforming growth factor β: amplified expression and secretion of mature and precursor polypeptides in Chinese hamster ovary cells. Mol Cell Biol 7:3418-3427, 1987.
82. Ghaneh P., Kawesha A., Evans JD, Neoptolemos JP: Molecular prognostic markers in pancreatic cancer. J Hepatobiliary Pancreat Surg 9:1-11, 2002.
83. Giannoudis PV, Psarakis S., Kanakaris NK, Pape HC: Biological enhancement of bone healing with bone morphogenetic protein-7 at clinical setting of pelvic girdle non-unions. Injury 34:S43-S48, 2007.
84. GlaxoSmithKline: [Fact sheet]. http://www.gsk.com/media/presskits/ASCO/global-tykerb-factsheet.pdf. Accessed 18 October 2009.
85. Gleixner KV, Rebuzzi L., Mayerhofer M., Gruze A., Hadzijusufovic E., Sonneck K., Vales A., Kneidinger M., Samorapoompichit P., Thaiwong T., Pickl WF, Yuzbasiyan-Gurkan V., Sillaber C., Willmann M., Valent P.: Synergistic antiproliferative effects of KIT tyrosine kinase inhibitors on neoplastic canine mast cells. Exp Hematol 35:1510-1521, 2007.
86. Gloe T., Sohn HY, Meininger GA, Pohl U.: Shear stress-induced release of basic fibroblast growth factor from endothelial cells is mediated by matrix interaction via integrin αvβ3. J Biol Chem 277:23453-23458, 2002.
87. Gospodarowicz D.: Purification of a fibroblast growth factor from bovine pituitary. J Biol Chem 250:2515-2520, 1975.
88. Grady WM, Myeroff LL, Swinler SE, Rajput A., Thiagalingam S., Lutterbaugh JD, Neumann A., Brattain MG, Chang J., Kim SJ, Kinzler KW, Vogelstein B., Willson JV, Markowitz S. Mutational inactivation of transforming growth factor β receptor type II in microsatellite stable colon cancers. Cancer Res 59:320-324, 1999.
89. Greten TF, Korangy F., Manns MP, Malek NP: Molecular therapy for the treatment of hepatocellular carcinoma. Br J Cancer 100:19-23, 2009.
90. Groenen LC, Nice EC, Burgess AW: Structure-function relationships for the EGF/TGF-α family of mitogens. Growth Factors 11:235-257, 1994.
91. Hahn SA, Schutte M., Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E., Weinstein CL, Fischer A., Yeo CJ, Hruban RH, Kern SE: DPC4: a candidate tumor suppressor gene at chromosome 18q21.1. Science 271:350-353, 1996.
92. Halper J., Moses HL: Purification and characterization of a novel transforming growth factor. Cancer Res 47:4552-4559, 1987.
93. Hamilton SR: Targeted therapy of cancer: new roles for pathologists in colorectal cancer. Mod Pathol 21:S23-S30, 2008.
94. Hansen LA, Alexander N., Hogan ME, Sundberg JP, Dlugosz A., Threadgill DW, Magnuson T., Yuspa SH: Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development. Am J Pathol 150:1959-1975, 1997.
95. Haupt JL, Donnelly BP, Nixon AJ: Effects of platelet-derived growth factor-BB on the metabolic function and morphologic features of equine tendon in explant culture. Am J Vet Res 67:1595- 1600, 2006.
96. He Z., Bateman A.: Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vitro. Cancer Res 59:3222-3229, 1999.
97. He Z., Ismail A., Kriazhev L., Sadvakassova G., Bateman A.: Progranulin (PC-cell-derived growth factor/acrogranin) regulates invasion and cell survival. Cancer Res 62:5590-5596, 2002.
98. He Z., Ong CH, Halper J., Bateman A.: Progranulin is a mediator of the wound response. Nat Med 9:225-229, 2003.
99. Heimark RL, Twardzik DR, Schwartz SM: Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets. Science 233:1078-1080, 1986.
100. Heldin CH, Eriksson U., Östman A: New members of the platelet-derived growth factor family of mitogens. Arch Biochem Biophys 398:284-290, 2002.
101. Heldin CH, Johnsson A., Wennergren S., Wernstedt C., Betsholtz C., Westermark B.: A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains. Nature 319:511-514, 1986.
102. Heldin CH, Östman A., Rönnstrand L.: Signal transduction via platelet-derived growth factor receptors. Biochim Biophys Acta 1378:F79-F113, 1998.
103. Heldin CH, Westermark B.: Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 79:1283- 1316, 1999.
104. Heng DY, Bukowski RM: Anti-angiogenic targets in the treatment of advanced renal cell carcinoma. Curr Cancer Drug Targets 8:676-682, 2008.
105. Hermanson M., Funa K., Koopmann J., Maintz D., Waha A., Westermark B., Heldin CH, Wiestler OD, Louis DN, von Deimling A., Nistér M.: Association of loss of heterozygosity on chromosome 17p with high platelet-derived growth factor α receptor expression in human malignant gliomas. Cancer Res 56:164-171, 1996.
106. Hiraga T., Nakamura H.: Imatinib mesylate suppresses bone metastases of breast cancer by inhibiting osteoclasts through the blockade of c-Fms signals. Int J Cancer 124:215-222, 2008.
107. Ho JC, Ip YC, Cheung ST, Lee YT, Chan KF, Wong SY, Fan ST: Granulin-epithelin precursor as a therapeutic target for hepatocellular carcinoma. Hepatology 47:1524-1532, 2008.
108. Houck KA, Leung DW, Rowland AM, Winer J., Ferrara N.: Dual regulation of vascular endothelial growth factor bioavailability by genetic and and proteolytic mechanisms. J Biol Chem 267:26031-26037, 1992.
109. Hsu S., Huang F., Hafez M., Winawer S., Friedman E.: Colon carcinoma cells switch their response to transforming growth factor β1 with tumor progression. Cell Growth Differ 6:1635- 1642, 1994.
110. Huh JI, Calvo A., Stafford J., Cheung M., Kumar R., Philp D., Kleinman HK, Green JE: Inhibition of VEGF receptors significantly impairs mammary cancer growth in C3(1)/Tag transgenic mice through antiangiogenic and non-antiangiogenic mechanism. Oncogene 24:790-800, 2005.
111. Hurwitz H., Fehrenbacher L., Novotny W., Cartwright T., Hainsworth J., Heim W., Berlin J., Baron A., Griffing S., Holmgren E., Ferrara N., Fyfe G., Rogers B., Ross R., Kabbinavar F.: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335-2342, 2004.
112. Ibbotson KJ, Harrod J., Gowen M., D'Sousa S., Smith DD, Winkler ME, Derynck R., Mundy GR: Human recombinant transforming growth factor α stimulates bone resorption and inhibits formation in vitro. Proc Natl Acad Sci U S A 83:2228-2232, 1986.
113. Igarashi M., Finch PW, Aaronson SA: Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7). J Biol Chem 273:13230-13235, 1998.
114. Issa JPM, Bentley Mvlb, Iyomasa MM, Sebald W., De Alburquerque RF: Sustained release carriers used to deliver bone morphogenetic proteins in the bone healing process. Anat Histol Embryol 37:181-187, 2008.
115. Jang JH, Shin KH, Park JG: Mutations in fibroblast growth factor receptor2 and fibroblast growth factor 3 genes associated with human gastric and colorectal cancers. Cancer Res 61:3541-3543, 2001.
116. Jena N., Martín-Seisdedos C., McCue P., Croce CM: BMP7 null mutation in mice: developmental defects in skeleton, kidney, and eye. Exp Cell Res 230:28-37, 1997.
117. Jenkins PJ, Bustin SA: Evidence for a link between IGF-I and cancer. Eur J Endocrinol 151:S17-S22, 2004.
118. Jhappan C., Stahle C., Harkins RN, Fausto N., Smith GH, Merlino GT: TGFα overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell 61:1137-1146, 1990.
119. Johnson & Johnson: Ethicon, Inc. Announces Revised Label For REGRANEX (becaplermin) Gel 0.01%. http://www.jnj.com/connect/news/all/20080606_114500. Accessed 19 October2009.
120. Johnsson A., Heldin CH, Westermark B., Wasteson A.: Platelet-derived growth factor: identification of constituent polypeptide chains. Biochem Biophys Res Commun 104:66-74, 1982.
121. Jones JI, Clemmons DR: Insulin-like growth factors and their binding proteins: biological actions. Endocrine Rev 16: 3-34, 1995.
122. Juul A.: Serum levels of insulin-like growth factor I and its binding protein in health and disease. Growth Horm IGF Res 13: 113-170, 2003.
123. Kamstock D., Elmslie R., Thamm D., Dow S.: Evaluation of a xenogeneic VEGF vaccine in dogs with soft tissue sarcoma. Cancer Immunol Immunother 56:1299-1309, 2007.
124. Kano MR, Bae Y., Iwata C., Morishita Y., Yashiro M., Oka M., Fujii T., Komuro A., Kiyona K., Kaminishi M., Hirakawa K., Ouchi Y., Nishiyama N., Kataoka K., Miyazono K.: Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of TGF-β signaling. Proc Natl Acad Sci U S A 104:3460-3465, 2007.
125. Karasik A., Menczer J., Pariente C., Kanety H.: Insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 are increased in cyst fluids of epithelial ovarian cancer. J Clin Endocrinol Metab 78:271-276, 1994.
126. Katayama R., Huelsmeyer MK, Marr AK, Kurzman ID, Thamm DH, Vail DM: Imatinib mesylate inhibits platelet-derived growth factor activity and increases chemosensitivity in feline vaccine-associated sarcoma. Cancer Chemother Pharmacol 54:25-33, 2004.
127. Kato Y., Asano K., Mogi T., Kutara K., Edamura K., Tsumagari S., Hasegawa A., Tanaka S.: Clinical significance of circulating vascular endothelial growth factor in dogs with mammary gland tumors. J Vet Med Sci 69:77-80, 2007.
128. Katoh M.: WNT and FGF gene clusters (review). Int J Oncol 21:1269-1273, 2002.
129. Katoh Y., Katoh M.: Comparative genomics on mammalian Fgf6-Fgf23 locus. Int J Mol Med 16:355-358, 2005.
130. Katoh Y., Katoh M.: Hedgehog signaling pathway and gastrointestinal stem cell signaling network. In J Mol Med 18:1019- 1023, 2006.
131. Kawaura Y., Tatsuzawa Y., Wakabayashi T., Ikeda N., Matsuda M., Nishihara S.: Immunohistochemical study of p53, c-erbB-2, and PCNA in Barrett's esophagus with dysplasia and adenocarcinoma arising from experimental acid or alkaline reflux model. J Gastroenterol 36:595-600, 2001.
132. Kelley KM, Schmidt KE, Berg L., Sak K., Galima MM, Gillespie C., Balogh, Hawayek A, Reyes JA, Jamison M.: Comparative endocrinology of the insulin-like growth factor-binding protein. J Endocrinol 175:3-18, 2002.
133. Kiefer P., Acland P., Pappin D., Peters G., Dickson C.: Competition between nuclear localization and secretory signals determine the subcellular fate of a single CUG-initiated form of FGF3. EMBO J 13:4126-4136, 1994.
134. Kingsley DM: The TGFβ superfamily: new members, new receptors, and new genetic tests of function on different organisms. Genes Dev 8:133-146, 1994.
135. Kochevar DT, Kochevar J., Garrett L.: Low level amplification of c-sis and c-myc in a spontaneous osteosarcoma model. Cancer Lett 53:213-222, 1990.
136. Kowanetz M., Ferrara N.: Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res 12:5018-5022, 2006.
137. Kramer A., Yang FC, Snodgrass P., Li X., Scammell TE, Davis FC, Weitz CJ: Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor. Science 294:2511-2515, 2001.
138. Kretzschmar M., Massagué J.: SMADs: mediators and regulators of TGF-β signaling. Curr Opin Genet Dev 8:103-111, 1998.
139. Kuhnert F., Tam BY, Sennino B., Gray JT, Yuan J., Jocson A., Nayak NR, Mulligan RC, McDonald DM, Kuo CJ: Soluble receptor-mediated selective inihibition of VEGFR and PDGFRβ signaling during physiologic and tumor angiogenesis. Proc Natl Acad Sci U S A 105:10185-10190, 2008.
140. Laping NJ, Everitt JI, Frazier KS, Burgert M., Portis MJ, Cadacio C., Gold LI, Walker CL: Tumor-specific efficacy of transforming-βRI inhibition in Eker rats. Clin Cancer Res 13:3087- 3099, 2007.
141. Lee CG, Kang HR, Homer RJ, Chupp G, Elias JA: Transgenic modeling of transforming growth factor-β1: role of apoptosis in fibrosis and alveolar remodeling. Proc Am Thorac Soc 3:418-423, 2006.
142. Lee DY, Kim SJ, Lee YC: Serum insulin-like growth factor (IGF-I)-I and IGF-binding proteins in lung cancer patients. J Korean Med Sci 14:401-404, 1998.
143. Lee S., Jilani SM, Nikolova GV, Carpiza D., Iruela-Arispe ML: Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol 168:681-691, 2005.
144. LeGrand EK: Preclinical promise of becaplermin (rhPDGF-BB) in wound healing. Am J Surg 176:48S-54S, 1998.
145. LeRoith D., Werner H., Beitner JD, Roberts CJ: Molecular and cellular aspects of the insulin-like factor I receptor. Endocrine Rev 16:143-163, 1995.
146. Letterio JJ, Geiser AG, Kulkarni AB, Roche NS, Sporn MB, Roberts AB: Maternal rescue of transforming growth factor-β1 null mice. Science 264:1936-1938, 1994.
147. Levine RA: Overexpression of the sis oncogene in a canine osteosarcoma cell line. Vet Pathol 39:411-412, 2002.
148. Levitt RJ, Georgescu MM, Pollak M.: PTEN-induction in U251 glioma cells decreases the expression of insulin-like growth factor binding protein-2. Biochem Biophys Res Commun 336:1056- 1061, 2005.
149. Lin HY, Wang XF, Ng- Eaton E., Weinberg RA, Lodish HF: Expression cloning of the TGF-β type II receptor, a functional transmembrane serine/threonine kinase. Cell 68:775-768, 1992.
150. London CA, Hannah AL, Zadovoskaya R., Chien MB, Kollias-Baker C., Rosenberg M., Downing S., Post G., Boucher J., Shenoy N., Mendel DB, McMahon G., Cherrington JM: Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res 9:2755-2768, 2003.
151. Lopez-Castilla F., Cheifetz S., Doody J., Andres JL, Lane WS, Massagué J.: Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-β receptor system. Cell 67:785-795, 1991.
152. Lu R., Serrero G.: Inhibition of PC-cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA MB-468. Proc Natl Acad Sci U S A 97:3993-3998, 2000.
153. Luetteke NC, Qiu TH, Peiffer RL, Oliver P., Smithies O., Lee DC: TGFα deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Cell 73:263-278, 1993.
154. MacEwen EG, Pastor J., Kutzke J., Tsan R., Kurzman ID, Thamm DH, Wilson M., Radinsky R.: IGF-1 receptor contributes to the malignant phenotype in human and canine osteosarcoma. J Cell Biochem 92:77-91, 2004.
155. Mann GB, Fowler KJ, Gabriel A., Nice EC, Williams RL, Dunn AR: Mice with a null mutation of the TGFα gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation. Cell 73:249-261, 1993.
156. Marics I., Adelaide J., Raybaud F., Mattei MG, Coulier F., Planche J., de Lapeyriere O., Birnbaum D.: Characterization of the HSTrelated FGF 6 gene, a new member of the fibroblast growth factor gene family. Oncogene 4:335-340, 1989.
157. Markowitz S., Wang J., Myeroff L., Parsons R., Sun L., Lutterbaugh J., Fan RS, Zborowska E., Kinzler KW, Vogelstein B., Brattain M., Willson JKV: Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science 268:1336-1338, 1995.
158. Marquardt H., Hunkapiller MW, Hood LE, Todaro GJ: Rat transforming growth factor type 1: structure and relation to epidermal growth factor. Science 223:1079-1082, 1984.
159. Massagué J.: TGF-β signal transduction (review). Annu Rev Biochem 67:753:791, 1998.
160. Mathew P., Thall PF, Wen S., Bucana C., Jones D., Horne E., Oh WK, Morris MJ, Lee YC, Logothetis CJ, Lin SH, Fidler IJ: Dynamic change in phosphorylated platelet-derived growth factor receptor in peripheral blood leukocytes following docetaxel therapy predicts progression-free and overall survival in prostate cancer. Br J Cancer 99:1426-1432, 2008.
161. Matsui Y., Halter SA, Holt JT, Hogan BLM, Coffey RJ: Development of mammary hyperplasia and neoplasia in MMTV-TGFα transgenic mice. Cell 61:1147-1155, 1990.
162. Matsumura N., Mandai M., Miyanishi M., Fukuhara K., Baba T., Higuchi T., Kariya M., Takakura K., Fujii S.: Oncogenic property of acrogranin in human uterine leiomyosarcoma: direct evidence of genetic contribution in in vivo tumorigenesis. Clin Cancer Res 12:1402-1411, 2006.
163. McCarthy HS, Williams JH, Davie MW, Marshall MJ: Platelet-derived growth factor stimulates osteoprotegerin production in osteoblastic cells. J Cell Physiol 218:350-354, 2009.
164. McCartney-Francis NL, Wahl SM: Transforming growth factor β: a matter of life and death. J Leukoc Biol 55:401-409, 1994.
165. McDonald NQ, Hendrickson WA: A structural superfamily of growth factors containing a cystine knot motif. Cell 73:421- 424, 1993.
166. Meinhardt UJ, Ho KK: Modulation of growth hormone action by sex steroids. Clin Endocrinol (Oxf) 65:413-422, 2006.
167. Messier C., Teutenberg K.: The role of insulin, insulin-like growth factor, and insulin-degrading enzyme in brain aging and Alzheimer's disease. Neural Plast 12:311-328, 2005.
168. Millanta F., Calandrella M., Citi S., Della Santa D., Poli A.: Overexpression of HER-2 in feline invasive mammary carcinomas: an immunohistochemical survey and evaluation of its prognostic potential. Vet Pathol 42:30-34, 2005.
169. Milovancev M., Muir P., Manley PA, Seeherman HJ, Schaefer S.: Clinical application of recombinant human bone morphogenetic protein-2 in 4 dogs. Vet Surg 36:132-140, 2007.
170. Mohan S., Baylink DJ: IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms. J Endocrinol 175:19-31, 2002.
171. Mol JA, Lantinga-van Leeuwen IS, van Garderen E., Selman PJ, Oosterlaken-Dijksterhuis MA, Schalken JA, Rijnberk A.: Mammary growth hormone and tumorigenesis-lessons from the dog. Vet Q 21:111-115, 1999.
172. Moser C., Schachtschneider P., Lang SA, Gaumann A., Mori A., Zimmermann J., Schlitt HJ, Geissler EK, Stoeltzing O. Inhibition of insulin-like growth factor-I receptor (IFG-IR) using NVP-AEW541, a small molecule kinase inhibitor, reduces orthotopic pancreatic cancer growth and angiogenesis. Eur J Cancer 44:1577-1586, 2008.
173. Muskavitch MA, Hoffmann FM: Homologs of vertebrate growth factors in Drosophila melanogaster and other invertebrates. Curr Top Dev Biol 24:289-328, 1990.
174. Myeroff LL, Parsons R., Kim SJ, Hedrick L., Cho KR, Orth K., Mathis M., Kinzler KW, Lutterbaugh J., Park K., Bang YJ, Young Lee HY, Park JG, Lynch HT, Roberts AB, Vogelstein B., Markowitz SD: A transforming growth factor β receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability. Cancer Res 55:5545- 5547, 1995.
175. Nahleh ZA: Molecularly targeted therapy in breast cancer: the new generation. Recent Pat Anticancer Drug Discov 3:100- 104, 2008.
176. Nelson MH, Dolder CR: Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors. Ann Pharmacother 40:261-269, 2006.
177. Novartis. About Gleevec. http://www.gleevec.com/info/ag/index.jsp. Accessed 19 October2009.
178. Okada-Ban M., Moens G., Thiery JP, Jouanneau J.: Nuclear 24 kD fibroblast growth factor (FGF)-2 confers metastatic properties on rat bladder carcinoma cells. Oncogene 18:6719-6724, 1999.
179. Okada-Ban M., Thiery JP, Jouanneau J.: Fibroblast growth factor-2. Int J Biochem Cell Biol 32:263-267, 2000.
180. O'kane S., Ferguson, MWJ: Transforming growth factor βs and wound healing. Int J Biochem Cell Biol 29:63-78, 1997.
181. Olsson AK, Dimberg A., Kreuger J., Claesson-Welsh J.: VEGF receptor signalling: in control of vascular function. Nat Rev Mol Cell Biol 7:359-371, 2006.
182. O'Reilly MS, Boehm T., Shing Y., Fukai N., Vasios G., Lane WS, Flynn E., Birkhead JR, Olsen BR, Folkman J.: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277-285, 1997.
183. Ornitz DM, Xu J., Colvin JS, McEwen DG, McArthur CA, Coulier F., Gao G., Goldfarb M.: Receptor specificity of the fibroblast growth factor family. J Biol Chem 271:15292-15297, 1996.
184. Parnell PG, Carter BJ, Halper J.: Identification of a membrane-associated receptor for transforming growth factor type e. J Receptor Signal Transduction Res 15:747-756, 1995.
185. Parnell PG, Wunderlich J., Carter B., Halper J.: Transforming growth factor type-e: amino acid analysis and partial amino acid sequence. Growth Factors 7:65-72, 1992.
186. Pasche B.: Role of transforming growth factor β in cancer. J Cell Physiol 186:153-168, 2001.
187. Patterson GI, Padgett RW: TGFβ-related pathways: roles in Caenorhabditis elegans development. Trends Genet 16:27-33, 2000.
188. Patyna S., Arrigoni C., Terron A., Kim TW, Heward JK, Vonderfecht SL, Denlinger R., Turnquist SE, Evering W.: Nonclinical safety evaluation of sunitinib: a potent inhibitor of VEGF, PDGF, KIT, FLT3, and RET receptors. Toxicol Pathol 36:905-916, 2008.
189. Paz K., Hadari YR: Targeted therapy of the insulin-like growth factor-1 receptor in cancer. Comb Chem High Throughput Screen 11:61-69, 2008.
190. Perks CM, Vernon EG, Rosendahl AH, Tonge D., Holly JM: IGF-II and IFGBP-2 differentially regulate PTEN in human breast cancer cells. Oncogene 26:5966-5972, 2007.
191. Peters MA, Mol JA, van Wolferen ME, Oosterlaken-Dijksterhuis MA, Teerds KJ, van Sluijs FJ: Expression of the insulin-like growth factor (IGF) system and steroidogenic enzymes in canine testis tumors. Reprod Biol Endocrinol 14:1-22, 2003.
192. Platt SR, Scase TJ, Adams V., Wieczorek L., Miller J., Adamo F., Long S.: Vascular endothelial growth factor expression in canine intracranial meningiomas and association with patient survival. J Vet Intern Med 20:663-668, 2006.
193. Plowman GD, Green JM, Neubauer MG, Buckley SD, McDonald VL, Todaro GD, Shoyab M.: The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth. J Biol Chem 267:13073-13078, 1992.
194. Podolsky DK: Healing the epithelium: solving the problem from two sides. J Gastroenterol 32:122-6, 1997.
195. Pollak MN, Schernhammer ES, Hankinson SE: Insulin-like growth factors and neoplasia. Nat Rev Cancer 4:505-518, 2004.
196. Pourgholami MH, Morris DL: Inhibitors of vascular endothelial growth factor in cancer. Cardiovasc Hematol Agents Med Chem 6:343-347, 2008.
197. Prats H., Kaghad M., Prats AC, Klagsbrun M., Lelias JM, Liauzun P., Chalon P., Tauber JP, Amalric F., Smith JA, Caput D.: High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons. Proc Natl Acad Sci U S A 86:1836-1840, 1989.
198. Qiu C., Lin D., Wang J., Li C., Deng G.: Expression and significance of PTEN and VEGF in canine mammary gland tumours. Vet Res Commun 32:463-472, 2008.
199. Qiu C., Lin DD, Wang HH, Qiao CH, Wang J., Zhang T.: Quantification of VEGF-C expression in canine mammary tumors. Aust Vet J 86:279-282, 2008.
200. Queiroga FL, Pérez-Alenza MD, Silvan G., Peña L., Lopes CS, Illera JC: Crosstalk between GH/IGF-I axis and steroid hormones (progesterone, 17β-estradiol) in canine mammary tumors. J Steroid Biochem Mol Biol 110:76-82, 2008.
201. Raines EW, Ross R.: Platelet-derived growth factor: I. High yield purification and evidence for multiple forms. J Biol Chem 9:5154-5160, 1982.
202. Ravitz MJ, Wenner CE: Cyclin-dependent kinase regulation during G1 phase and cell cycle regulation by TGF-β. Adv Cancer Res 71:165-207, 1997.
203. Re RN: Toward a theory of intracrine hormone action. Regul Pept 106:1-6, 2002.
204. Rebuzzi L., Willmann M., Sonneck K., Gleixner KV, Florian S., Kondo R., Mayerhofer M., Vales A., Gruze A., Picki WF, Thalhammer JG, Valent P.: Detection of vascular endothelial growth factor (VEGF) and VEGF receptors Flt-1 and KDR in canine mastocytoma cells. Vet Immunol Immunopathol 115:320-333, 2006.
205. Red-Horse K., Crawford Y., Shojaei F., Ferrara N.: Endothelium-microenvironment interactions in the developing embryo and in the adult. Dev Cell 12:181-194, 2007.
206. Reddy K., Cao Y., Zhou Z., Yu L., Jia SF, Kleinerman ES: VEGF165 expression in the tumor microenvironment influences the differentiation of bone marrow-derived pericytes that contribute to the Ewing's sarcoma vasculature. Angiogenesis 11:257-267, 2008.
207. Reichardt P.: Novel approaches to imanitib- and sunitinib-resistant GIST. Curr Oncol Rep 10:344-349, 2008.
208. Ricort JM, Binoux M.: Insulin-like growth factor-binding protein-3 activates a phosphotyrosine phosphatase: effects on the insulin-like growth factor signaling pathway. J Biol Chem 277:19448-19454, 2002.
209. Rikhof B., de Jong S., Suurmeijer AJ, Meijer C., van der Graaf WT: The insulin-like growth factor system and sarcomas. J Pathol 217:469-482, 2009.
210. Roberts AB, Lamb LC, Newton DL, Sporn MB, DeLarco JE, Todaro GJ: Transforming growth factors: isolation of polypeptides from virally and chemically transformed cell by acid/ethanol extraction. Proc Natl Acad Sci U S A 77:3494-3498, 1980.
211. Roberts AB, Sporn MB: Physiological actions and clinical application of transforming growth factor-β (TGF-β). Growth Factors 8:1-9, 1993.
212. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Loitta LA, Falanga VA, Kehrl JH, Fauci AS: Transforming growth factor type-beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A 83:4167-4171, 1986.
213. Roberts AB, Tian F., DaCosta Byfield S., Stuelten C., Ooshima A., Saika S., Flanders KC: Smad3 is key to TGF-β-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis. Cyt Growth Factor Rev 17:19-27, 2006.
214. Robson MC, Phillips LG, Lawrence WT, Bishop JB, Younger-man JS, Hayward PG, Broemeling LD, Heggers JP: The safety and effect of topically applied recombinant basic fibroblast growth factor on the healing of chronic pressure sores. Ann Surg 216:401-406, 1992.
215. Robson MC, Phillips LG, Thomason A., Robson LE, Pierce GF: Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet 339:23-25, 1992.
216. Rossmeisl JH, Duncan RB, Huckle WR, Troy GC: Expression of vascular endothelial growth factor in tumors and plasma from dogs with primary intracranial neoplasm. Am J Vet Res 68:1239-1245, 2007.
217. Sakamoto H., Mori M., Taira M., Yoshida T., Matsukawa S., Shimizu S., Sekiguchi M., Terada M., Sugimura T.: Transforming gene from human stomach cancers and a noncancerous portion of stomach mucosa. Proc Natl Acad Sci U S A 83:3997-4001, 1986.
218. Samani AA, Yakar S., LeRoith D., Brodt P.: The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev 28:20-47, 2007.
219. Sandgren EP, Luetteke NC, Palmiter RD, Brinster RL, Lee DC: Overexpression of TGFα in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell 61:1121-1135, 1990.
220. Schechter AL, Stern DF, Vaidyanathan L., Decker SJ, Drebin JA, Greene MI, Weinberg RA: The new oncogene: an erbB related gene encoding a 185,000-Mr tumour antigen. Nature 312:513- 516, 1984.
221. Schilder RJ, Sill MW, Lee RB, Shaw TJ, Senterman MK, Klein-Szanto AJ, Miner Z., Vanderhyden BC: Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: gynecologic oncology group study. J Clin Oncol 26:3418-3425, 2008.
222. Schlessinger J.: Regulation of cell growth and transformation by the epidermal growth factor receptor. Adv Exp Med Biol 234:65-73, 1988.
223. Schlessinger J., Ullrich A., Honegger AM, Molenaar MH: Signal transduction by epidermal growth factor receptor. Cold Spring Harb Symp Quant Biol 53(Pt1):515-519, 1988.
224. Schoeffner DJ, Matheny SL, Akahane T., Factor V., Berry A., Merlino G., Thorgeirsson UP: VEGF contributes to mammary tumor growth in transgenic mice through paracrine and autocrine mechanisms. Lab Invest 85:608-623, 2005.
225. Schreiber AB, Winkler ME, Derynck R.: Transforming growth factor-α: a more potent angiogenic mediator than epidermal growth factor. Science 232:1250-1253, 1986.
226. Schultz-Cherry S., Chen H., Mosher DP, Misenheimer TM, Krutzsch HC, Roberts DD, Murphy-Ullrich JE: Regulation of transforming growth factor-β activation by discrete sequences of thrombospondin 1. J Biol Chem 270:7304-7310, 1995.
227. Shimada T., Mizutani S., Muto T., Yoneya T., Hino R., Takeda S., Takeuchi S., Takeuchi Y., Fujita T., Fukumoto S., Yamashita T.: Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci U S A 98:6500-6505, 2001.
228. Shin JT, Opalenik SR, Wehby JN, Mahesh VK, Jackson A., Tarantini F., Maciag T., Thompson JA: Serum starvation induces the extracellular appearance of FGF-1. Biochim Biophys Acta 1312:27-38, 1996.
229. Shoyab M., McDonald VL, Byles C., Todaro GJ, Plowman GD: Epithelins 1 and 2: isolation and characterization of two cysteine-rich growth-modulating proteins. Proc Natl Acad Sci U S A 87:7912-7916, 1990.
230. Sirvent N., Maire G., Pedeutour F.: Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment. Genes Chromosomes Cancer 37:1-19, 2003.
231. Skov Olsen P.: Role of epidermal growth factor in gastroduodenal mucosal protection. J Clin Gastroenterol 10:S146-S151, 1988.
232. So AI, Levitt RJ, Eigl B., Fazli L., Muramaki M., Leung S., Cheang MC, Nielsen TO, Gleave M., Pollak M.: Insulin-like growth factor binding protein-2 is a novel therapeutic target associated with breast cancer. Clin Cancer Res 14:6944-6954, 2008.
233. Sporn MB, Todaro GJ: Autocrine secretion and malignant transformation of cells. N Engl J Med 303:878-880, 1980.
234. Steed DL: Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity ulcers. Plast Reconstr Surg 117:143S-149S, 2006.
235. Steiner DF, Rubenstein AH: Proinsulin C-peptide: biological activity? Science 277:531-532, 1997.
236. Stetler-Stevenson WG: The tumor microenvironment: regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2. Cancer Metastasis Rev 27:57-66, 2008.
237. Stockmann C., Doedens A., Weidemann A., Zhang N., Takeda N., Greenberg JI, Cheresh DA, Johnson RS: Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis. Nature 456:814-818, 2008.
238. Stoica G., Tasca SI, Kim HT: Point mutation of neu oncogene in animal peripheral nerve sheath tumor. Vet Pathol 38:679-688, 2001.
239. Stroobant P., Waterfield MD: Purification and properties of porcine platelet-derived growth factor. EMBO J 2:2963-2967, 1984.
240. Tai AL, Sham JS, Xie D., Fang Y., Wu YL, Hu L., Deng W., Tsao GS, Qiao GB, Cheung AL, Guan XY: Co-expression of fibroblast growth factor 3 and epidermal growth factor receptor is correlated with the development of nonsmall cell lung carcinoma. Cancer 106:146-155, 2006.
241. Takahashi H., Shibuya M.: The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond) 108:227-241, 2005.
242. Takaku K., Oshima M., Miyoshi H., Matsui M., Seldin MF, Taketo MM: Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes. Cell 92:645-656, 1998.
243. Takehara K., LeRoy EC, Grotendorst GR: TGF-beta inhibition of endothelial cell proliferation: alteration of EGF binding and EGFinduced growth regulatory gene expression. Cell 49:415-422, 1987.
244. Tang B., Böttinger EP, Jakowlew SB, Bagnall KM, Mariano J., Anver MR, Letterio JJ, Wakefield LM: Transforming growth factor-β1 is a new form of tumor suppressor with true haploid insufficiency. Nat Med 4:802-807, 1998.
245. Tanno B., Mancini C., Vitali R., Mancuso M., Heather P., McDowell HP, Dominici C., Raschellà G.: Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. Clin Cancer Res 12:6772-6780, 2006.
246. Taverna S., Ghersi G., Ginestra A., Rigogliuso S., Pecorella S., Alaimo G., Saladino F., Dolo V., Dell'Era P., Pavan A., Pizzolanti G., Mignatti P., Presta M., Vittorelli ML: Shedding of membrane vesicles mediates fibroblast growth factor-2 release from cells. J Biol Chem 278:51911-51919, 2003.
247. Thamm DH, Dickerson EB, Akhtar N., Lewis R., Auerbach R., Helfand SC, MacEwen EG: Biological and molecular characterization of a canine hemangiosarcoma-derived cell line. Res Vet Sci 81:76-86, 2006.
248. Thiagalingam S., Lengauer C., Leach FS, Schutte M., Hahn SA, Overhauser J., Wilson JK, Markowitz S., Hamilton SR, Kern SE, Kinzler KW, Vogelstein B.: Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nat Genet 13:343-346, 1996.
249. Thomas-Mudge RJ, Okada-Ban M., Vandenbroucke F., Vincent-Salomon A., Girault JM, Thiery JP, Jouanneau J.: Nuclear FGF-2 facilitates cell survival in vitro and during establishment of metastases. Oncogene 23:4771-4779, 2004.
250. Tolkatchev D., Malik S., Vinogradova A., Wang P., Chen Z., Xu P., Bennett HPJ, Bateman J.: Structure dissection of human progranulin identifies well-folded granulin/epithelin modules with unique functional activities. Protein Sci 17:711-724, 2008.
251. Tricoli JV, Rall LB, Karakousis CP, Herrera L., Petrelli NJ, Bell GI, Shows TB: Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas. Cancer Res 46:6169-6173, 1986.
252. Tropepe V., Craig CG, Morshead CM, van der Kooy D.: Transforming growth factor-α null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma. J Neurosci 17:7850-7859, 1997.
253. Tucker RF, Shipley GD, Moses HL, Holley RW: Growth inhibitor from BSC-1 cells closely related to platelet type β transforming growth factor. Science 226:705-707, 1984.
254. Uhrbom L., Hesselager G., Nistér M., Westermark B.: Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirus. Cancer Res 58:5275-5279, 1998.
255. Ullrich A., Sclessinger J.: Signal transduction by receptors with tyrosine kinase activity. Cell 61:203-212, 1990.
256. Urist M.: Bone: formation by autoinduction. Science 150:893- 899, 1965.
257. Van de Geer P., Hunter T., Lindberg RA: Receptor protein-tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol 10:251-337, 1994.
258. Villanueva A., Garcia C., Paules AB, Vincente M., Megias M., Reyes G., Devillalonga P., Agell N., Lluis F., Bachs O., Capella G.: Disruption of the antiproliferative TGF-β signaling pathways in human pancreatic cancer cells. Oncogene 17:1969-1978, 1998.
259. Wang J., Sun LZ, Myeroff L., Wang XF, Gentry LE, Yan JH, Liang JR, Zborowska E., Markowitz S., Willson JKV, Brattain MG: Demonstration that mutation of the type II transforming growth factor β receptor inactivates its tumor suppressor activity in replication error-positive colon carcinoma cells. J Biol Chem 270:22044-22049, 1995.
260. Waterfield MD, Scrace GT, Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin CH, Huang JS, Deuel TF: Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature 304:35-39, 1983.
261. Welm BE, Freeman KW, Chen M., Contreras A., Spencer DM, Rosen JM: Inducible dimerization of FGFR1: development of a mouse model to analyze progressive transformation of the mammary gland. J Cell Biol 157:703-714, 2002.
262. Wergin MC, Kaser-Hotz B.: Plasma vascular endothelial growth factor (VEGF) measured in seventy dogs with spontaneously occurring tumours. In Vivo 18:15-19, 2004.
263. Wetterau LA, Moore MG, Lee KW, Shim ML, Cohen P.: Novel aspects of the insulin-like growth factor binding proteins. Mol Genet Metab 68:161-181, 1999.
264. Wheatley-Price P., Shepherd FA: Targeting angiogenesis in the treatment of lung cancer. J Thorac Oncol 3:1173-1184, 2008.
265. Wolfesberger B., Guija de Arespacohaga A., Willmann M., Gerner W., Miller I., Schwendenwein I., Kleiter M., Egerbacher M., Thalhammer JG, Muellauer L., Skalicky M., Walter I.: Expression of vascular endothelial growth factor and its receptors in canine lymphoma. J Comp Pathol 137:30-40, 2007.
266. Wrobel G., Roerig P., Kokocinski F., Neben K., Hahn, M., Reifenberger G., Lichter P.: Microarray-based gene expression profiling of benign, atypical and anaplastic meningiomas identifies novel genes associates with meningioma progression. Int J Cancer 114:249-256, 2005.
267. Xiao S., Nalabolu SR, Aster JC, Ma J., Abruzzo L., Jaffe ES, Stone R., Weissman SM, Hudson TJ, Fletcher JA: FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Nat Genet 18:84-87, 1998.
268. Yakar S., Bouxsein ML, Canalis R., Sun H., Glatt V., Grundberg C., Cohen P., Hwang D., Boisclair Y., Leroith D., Rosen CJ: The ternary IGF complex influnces postnatal bone acquisition and the skeletal response to intermittent parathyroid hormone. J Endocrinol 189:289-299, 2006.
269. Yasui W., Oue N., Aung PP, Matsumura S., Shutoh M., Nakayama H.: Molecular-pathological prognostic factors of gastric cancer: a review. Gastric Cancer 8:86-94, 2005.
270. Yonemaru K., Sakai H., Murakami M., Yanai T., Maseqi T.: Expression of vascular endothelial growth factor, basic fibroblast growth factor, and their receptors (flt-1, flk-1, and flg-1) in canine vascular tumors. Vet Pathol 43:971-980, 2006.
271. Yoshida MC, Wada M., Satoh H., Yoshida T., Sakamoto H., Miyagawa K., Yokota J., Koda T., Kakinuma M., Sugimura T., Terada M.: Human HST1 (HSTF1) gene maps to chromosome band 11q13 and coamplifies with the INT2 gene it human cancer. Proc Natl Acad Sci U S A 85:4861-4864, 1988.
272. Zaharieva BM, Simon R., Diener PA, Ackermann D., Maurer R., Aulund G., Knonagel H., Rist M., Wilber K., Hering F., Schonenberger A., Flury R., Jager P., Fehr JL, Mihatsch, Gasser T., Sauter G., Toncheva DI: High-throughput tissue microarray analysis of 11q13 gene amplification (CCND1, FGF3, FGF4, EMS1) in urinary bladder cancer. J Pathol 201:603-608, 2003.
273. Zehe C., Engling A., Wegehingel S., Schäfer, Nickel W: Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2. Proc Natl Acad Sci U S A 103:15479-15484, 2006.
274. Zhang X., Ibrahimi OA, Olsen SK, Umemori H., Mohammadi M., Ornitz DM: Receptor specificity of the fibroblast growth factor family: the complete mammalian FGF family. J Biol Chem 281:15694-15700, 2006.
275. Zhou J., Bondy C.: Anatomy of the insulin-like growth factor system in the human testis. Fertil Steril 60:897-904, 1993.
276. Zhu J., Nathan C., Jin W., Sim D., Ashcroft GS, Wahl SM, Lacomix L., Erljument-Bromage H., Tempst P., Wright CD, Ding A.: Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell 111:867-878, 2002.
277. Zhu X., Stergiopoulos K., Wu S.: Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncol 48:9-17, 2009.
278. Zhu Y., Richardson JA, Parada LF, Graff JM: Smad3 mutant mice develop metastatic colorectal. Cell 94:703-714, 1998.