PDGF/PDGFR signaling and targeting in cancer growth and progression: Focus on tumor microenvironment and cancer-associated fibroblasts

Current Pharmaceutical Design

Volumn 20, Issue 17, 2014, Pages 2843-2848

  Gialeli, Chrisostomi ^a,d   Nikitovic, Dragana ^b   Kletsas, Dimitris ^c   Theocharis, Achilleas D ^a   Tzanakakis, George N ^b   Karamanos, Nikos K ^a,d  

^a UNIVERSITY OF PATRAS   (Greece)

^b UNIVERSITY OF CRETE   (Greece)

^c INSTITUTE OF NANOSCIENCE AND NANOTECHNOLOGY   (Greece)

^d INSTITUTE OF CHEMICAL ENGINEERING SCIENCES   (Greece)

Author keywords

Cancer targeting; Cancer associated fibroblasts; Cell signaling; Extracellular matrix; PDGF; Tumor microenvironment

Indexed keywords

GROWTH FACTOR; IMATINIB; MATRIX METALLOPROTEINASE; PACLITAXEL; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR A; PLATELET DERIVED GROWTH FACTOR AB; PLATELET DERIVED GROWTH FACTOR B; PLATELET DERIVED GROWTH FACTOR BB; PLATELET DERIVED GROWTH FACTOR RECEPTOR; REACTIVE OXYGEN METABOLITE; SORAFENIB; SUNITINIB; VASCULOTROPIN; VASCULOTROPIN C;

CANCER CELL; CANCER GROWTH; CANCER RESEARCH; CELL ACTIVATION; CELL ADHESION; CELL TRANSDIFFERENTIATION; DRUG TARGETING; EPITHELIAL MESENCHYMAL TRANSITION; EPITHELIUM CELL; FIBROBLAST; GAP JUNCTION; GENE EXPRESSION PROFILING; HOMEOSTASIS; HUMAN; HYPOXIA; MACROMOLECULE; MACROPHAGE; MOLECULAR WEIGHT; MYOFIBROBLAST; NONHUMAN; PARACRINE SIGNALING; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SKIN CARCINOGENESIS; STROMA; SYNTHESIS; TUMOR MICROENVIRONMENT; TUMOR VOLUME; UPREGULATION; BIOLOGICAL MODEL; DRUG EFFECTS; EXTRACELLULAR MATRIX; METABOLISM; MOLECULARLY TARGETED THERAPY;

EXTRACELLULAR MATRIX; FIBROBLASTS; HUMANS; MODELS, BIOLOGICAL; MOLECULAR TARGETED THERAPY; PLATELET-DERIVED GROWTH FACTOR; RECEPTORS, PLATELET-DERIVED GROWTH FACTOR; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT;

EID: 84903708565     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/13816128113199990592     Document Type: Review

References (94)

1. Fidler IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 2003; 3: 453-8.
2. Micke P, Ostman A. Tumour-stroma interaction: cancer-associated fibroblasts as novel targets in anti-cancer therapy? Lung Cancer. 2004; 45(2): S163-75.
3. Shimoda M, Mellody KT, Orimo A. Carcinoma-associated fibroblasts are a rate-limiting determinant for tumour progression. Semin Cell Dev Biol. 2010; 21(1): 19-25.
4. Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature 2001; 411: 375-9.
5. Kalluri R. Basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer 2003; 3: 422-33.
6. Theocharis AD, Skandalis SS, Tzanakakis GN, Karamanos NK. Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting. FEBS J 2010; 277: 3904-23.
7. Gialeli Ch, Theocharis AD, Karamanos NK. Matrix metalloproteinases in health and disease: roles in cancer progression and their pharmacological targeting. FEBS J 2011; 278: 16-27
8. Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 1986; 315 (26): 1650-59.
9. Elenbaas B, Weinberg RA. Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation. Exp Cell Res 2001; 264(1): 169-84.
10. Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression. Nature 2004; 432(7015): 332-7.
11. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer. 2006 6(5): 392-401.
12. Radisky DC, Kenny PA, Bissell MJ. Fibrosis and cancer: do myofibroblasts come also from epithelial cells via EMT? J Cell Biochem 2007; 101(4): 830-9.
13. Zeisberg EM, Potenta S, Xie L, Zeisberg M, Kalluri R. Discovery of endothelial to mesenchymal transition as a source for carcinomaassociated fibroblasts. Cancer Res 2007; 67(21): 10123-8.
14. Spaeth EL, Dembinski JL, Sasser AK, et al F. Mesenchymal stem cell transition to tumorassociated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS One 2009; 4(4): e4992
15. Kalluri R and Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119(6): 1420-8
16. Paunescu V, Bojin FM, Tatu CA, et al. Tumour-associated fibroblasts and mesenchymal stem cells: more similarities than differences. J Cell Mol Med. 2011; 15(3): 635-46.
17. Lohr M, Schmidt C, Ringel J, et al. Transforming growth factorbeta1 induces desmoplasia in an experimental model of human pancreatic carcinoma. Cancer Res 2001; 61(2): 550-5.
18. Bronzert DA, Pantazis P, Antoniades HN, et al. Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines. Proc Natl Acad Sci USA 1987; 84(16): 5763-67.
19. Shao ZM, Nguyen M, Barsky SH. Human breast carcinoma desmoplasia is PDGF initiated. Oncogene 2000; 19(38): 4337-45.
20. Strutz F, Zeisberg M, Hemmerlein B, Sattler B, Hummel K, Becker V, Muller GA. Basic fibroblast growth factor expression is increased in human renal fibrogenesis and may mediate autocrine fibroblast proliferation. Kidney Int 2000; 57(4): 1521-38.
21. Ellis MJ, Singer C, Hornby A, et al. Insulin-like growth factor mediated stromal-epithelial interactions in human breast cancer. Breast Cancer Res Treat 1994; 31: 249-61.
22. Powell DW, Mifflin RC, Valentich JD, et al. Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol 1999; 277: C1-9.
23. Cat B, Stuhlmann D, Steinbrenner H, et al. Enhancement of tumor invasion depends on transdifferentiation of skin fibroblasts mediated by reactive oxygen species. J Cell Sci 2006; 119(Pt 13): 2727-38.
24. Stuhlmann D, Steinbrenner H, Wendlandt B, Mitic D, Sies H, Brenneisen P. Paracrine effect of TGF-beta1 on downregulation of gap junctional intercellular communication between human dermal fibroblasts. Biochem Biophys Res Commun 2004; 319(2): 321-6.
25. Rønnov-Jessen L, Petersen OW. Induction of α-smooth muscle actin by transforming growth factor-β1 in quiescent human breast gland fibroblasts: implications for myofibroblast generation in breast neoplasia. Lab Invest 1993; 68: 696-707.
26. Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor β. J Exp Med 1987; 165: 251-6.
27. Sappino A, Schurch W, Gabbiani G. Biology of disease, differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest 1990; 63: 144-61.
28. Clement S, Stouffs M, Bettiol E, et al. Expression and function of alpha-smooth muscle actin during embryonic-stem-cell-derived cardiomyocyte differentiation. J Cell Sci 2007; 120: 229-38.
29. Ronnov-Jessen L, Petersen OW. A function for filamentous alphasmooth muscle actin: retardation of motility in fibroblasts. J Cell Biol 1996; 134: 67-80.
30. Cirri P, Chiarugi P. Cancer associated fibroblasts: the dark side of the coin. Am J Cancer Res 2011; 1(4): 482-97.
31. Orimo A, Gupta PB, Sgroi DC, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 2005; 121: 335-48.
32. Wang W, Li Q, Yamada T, et al. Crosstalk to stromal fibroblasts induces resistance of lung cancer to epidermal growth factor receptor tyrosine kinase inhibitors. Clin Cancer Res 2009; 15(21): 6630-8.
33. Jedeszko C, Victor BC, Podgorski I, Sloane BF. Fibroblast hepatocyte growth factor promotes invasion of human mammary ductal carcinoma in situ. Cancer Res 2009; 69(23): 9148-55.
34. van Zijl F, Mair M, Csiszar A, et al. Hepatic tumor-stroma crosstalk guides epithelial to mesenchymal transition at the tumor edge. Oncogene 2009; 28: 4022-33.
35. Augsten M, Hagglof C, Olsson E, et al. CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth. Proc Natl Acad Sci USA 2009; 106(9): 3414-9.
36. Pietras K, Sjöblom T, Rubin K, Heldin CH, Ostman A. PDGF receptors as cancer drug targets. Cancer Cell 2003; 3(5): 439-43.
37. Pantazis P, Lanfrancone L, Pelicci PG, Dalla-Favera R, Antoniades HN. Human leukemia cells synthesize and secrete proteins related to platelet-derived growth factor. Proc Natl Acad Sci USA 1986; 83(15): 5526-30.
38. Pantazis P, Pelicci PG, Dalla-Favera R, Antoniades HN. Synthesis and secretion of proteins resembling platelet-derived growth factor by human glioblastoma and fibrosarcoma cells in culture. Proc Natl Acad Sci USA 1985; 82(8): 2404-8.
39. Sitaras NM, Sariban E, Bravo M, Pantazis P, Antoniades HN. Constitutive production of platelet-derived growth factor-like proteins by human prostate carcinoma cell lines. Cancer Res 1988; 48(7): 1930-5.
40. Sariban E, Sitaras NM, Antoniades HN, Kufe DW, Pantazis P. Expression of platelet-derived growth factor (PDGF)-related transcripts and synthesis of biologically active PDGF-like proteins by human malignant epithelial cell lines. J Clin Invest 1988; 82(4): 1157-64.
41. Pontén F, Ren Z, Nistér M, Westermark B, Pontén J. Epithelialstromal interactions in basal cell cancer: the PDGF system. J Invest Dermatol 1994; 102(3): 304-9.
42. Kawai T, Hiroi S, Torikata C. Expression in lung carcinomas of platelet-derived growth factor and its receptors. Lab Invest 1997; 77(5): 431-6.
43. Tejada ML, Yu L, Dong J, et al. Tumor-driven paracrine plateletderived growth factor receptor alpha signaling is a key determinant of stromal cell recruitment in a model of human lung carcinoma. Clin Cancer Res 2006; 12(9): 2676-88.
44. Bhardwaj B, Klassen J, Cossette N, et al. Localization of plateletderived growth factor beta receptor expression in the periepithelial stroma of human breast carcinoma. Clin Cancer Res 1996; 2(4): 773-82.
45. Sundberg C, Branting M, Gerdin B, Rubin K. Tumor cell and connective tissue cell interactions in human colorectal adenocarcinoma. Transfer of platelet-derived growth factor-AB/BB to stromal cells. Am J Pathol 1997; 151(2): 479-92.
46. Skobe M, Fusenig NE. Tumorigenic conversion of immortal human keratinocytes through stromal cell activation. Proc Natl Acad Sci USA 1998; 95(3): 1050-5.
47. Forsberg K, Valyi-Nagy I, Heldin CH, Herlyn M, Westermark B. Platelet-derived growth factor (PDGF) in oncogenesis: development of a vascular connective tissue stroma in xenotransplanted human melanoma producing PDGF-BB. Proc Natl Acad Sci USA 1993; 90(2): 393-7.
48. Anderberg C, Li H, Fredriksson L, et al. Paracrine signaling by platelet-derived growth factor-CC promotes tumor growth by recruitment of cancer-associated fibroblasts. Cancer Res 2009; 69(1): 369-78.
49. Westermark B, Heldin CH. Platelet-derived growth factor. Structure, function and implications in normal and malignant cell growth. Acta Oncol 1993; 32(2): 101-5.
50. Östman A. PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev 2004; 15(4): 275-86.
51. Slomovitz BM, Broaddus RR, Schmandt R, et al. Expression of imatinib mesylate-targeted kinases in endometrial carcinoma. Gynecologic Oncol 2004; 95(1): 32-6.
52. Schmandt RE, Broaddus R, Lu KH, et al. Expression of c-ABL, c-KIT, and platelet-derived growth factor receptor-β in ovarian serous carcinoma and normal ovarian surface epithelium. Cancer 2003; 98(4): 758-64.
53. Lederle W, Stark HJ, Skobe M, Fusenig NE, Mueller MM. Plateletderived growth factor-BB controls epithelial tumor phenotype by differential growth factor regulation in stromal cells. Am J Pathol 2006; 169(5): 1767-83.
54. Mueller M and Fusenig N. Tumor-stroma interactions directing phenotype and progression of epithelial skin tumor cells. Differentiation 2002; 70: 486-97.
55. Ruan K, Song G, Ouyang G. Role of hypoxia in the hallmarks of human cancer. J Cell Biochem 2009; 107: 1053-62.
56. Lau CK, Yang ZF, Ho DW, et al. An Akt/hypoxia-inducible factor-1alpha/platelet-derived growth factor-BB autocrine loop mediates hypoxia-induced chemoresistance in liver cancer cells and tumorigenic hepatic progenitor cells. Clin Cancer Res 2009; 15: 3462-71
57. Finak G, Bertos N, Pepin F, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 2008; 14: 518-27.
58. Ostman A, Augsten M. Cancer-associated fibroblasts and tumor growth--bystanders turning into key players Curr Opin Genet Dev 2009; 19(1): 67-73.
59. Jain S, Chakraborty G, Bulbule A, Kaur R, Kundu GC. Osteopontin: an emerging therapeutic target for anticancer therapy. Expert Opin Ther Targets 2007; 11(1): 81-90.
60. Willenberg A, Saalbach A, Simon JC, Anderegg U. Melanoma Cells Control HA Synthesis in Peritumoral Fibroblasts via PDGFAA and PDGF-CC: Impact on Melanoma Cell Proliferation. J Invest Dermatol 2012; 132(2): 385-93.
61. Li L, Asteriou T, Bernert B, Heldin CH, Heldin P. Growth factor regulation of hyaluronan synthesis and degradation in human dermal fibroblasts: importance of hyaluronan for the mitogenic response of PDGF-BB. Biochem J 2007; 404(2): 327-36.
62. Zhang L, Underhill CB, Chen L. Hyaluronan on the surface of tumour cells is correlated with metastatic behaviour. Cancer Res 1995; 55, 428-33.
63. Mukaratirwa S, Koninkx JF, Gruys E, Nederbragt H. Mutual paracrine effects of colorectal tumour cells and stromal cells: modulation of tumour and stromal cell differentiation and extracellular matrix component production in culture. Int J Exp Pathol 2005; 86(4): 219-29.
64. Wight TN. Versican: a versatile extracellular matrix proteoglycan in cell biology. Curr Opin Cell Biol 2002; 14: 617-23.
65. Ricciardelli C, Brooks JH, Suwiwat S. et al. Regulation of stromal versican expression by breast cancer cells and importance to relapse-free survival in patients with nodenegative primary breast cancer. Clin Cancer Res 2002; 8: 1054-60.
66. Touab M, Villena J, Barranco C, Arumi-Uria M, Bassols A. Versican is differentially expressed in human melanoma and may play a role in tumor development. Am J Pathol 2002; 160: 549-57.
67. Skandalis SS, Labropoulou VT, Ravazoula P, et al. Versican but not decorin accumulation is related to malignancy in mammographically detected high density and malignant-appearing microcalcifications in non-palpable breast carcinomas. BMC Cancer 2011; 11: 314.
68. Labropoulou VT, Theocharis AD, Ravazoula P, et al. Versican but not decorin accumulation is related to metastatic potential and neovascularization in testicular germ cell tumours. Histopathology 2006; 49(6): 582-93.
69. Oyama F, Hirohashi S, Sakamoto M, et al. Coordinate oncodevelopmental modulation of alternative splicing of fibronectin premessenger RNA at ED-A, ED-B, and CS1 regions in human liver tumors. Cancer Res 1993; 53: 2005-11.
70. Serini G, Bochaton-Piallat ML, Ropraz P, et al. The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-β1. J Cell Biol 1998; 142: 873-81.
71. Brouty-Boyé D, Magnien V. Myofibroblast and concurrent ED-B fibronectin phenotype in human stromal cells cultured from nonmalignant and malignant breast tissue. Eur J Cancer 1994; 30A(1): 66-73.
72. Kimura A, Katoh O, Hyodo H, Kuramoto A, Satow Y. Leuk Platelet derived growth factor expression, myelofibrosis and chronic myelogenous leukemia. Lymphoma 1995; 18(3-4): 237-42.
73. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002; 2: 161-174.
74. Kaminski A, Hahne JC, Haddouti el-M, Florin A, Wellmann A, Wernert N. Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts. Int J Mol Med 2006; 18(5): 941-50.
75. Têtu B, Trudel D, Wang CS. Proteases by reactive stromal cells in cancer: an attractive therapeutic target. Bull Cancer 2006; 93(9): 944-8.
76. Jain RK. Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. J Control Release 2001; 74(1-3): 7-25.
77. Sajja HK, East MP, Mao H, Wang YA, Nie S, Yang L. Development of multifunctional nanoparticles for targeted drug delivery and noninvasive imaging of therapeutic effect. Curr Drug Discov Technol 2009; 6(1): 43-51.
78. Parajó Y, D'Angelo I, Welle A, Garcia-Fuentes M, Alonso MJ. Hyaluronic acid/Chitosan nanoparticles as delivery vehicles for VEGF and PDGF-BB. Drug Deliv 2010; 17(8): 596-604.
79. Roussidis AE, Theocharis AD, Tzanakakis GN, Karamanos NK. The importance of c-Kit and PDGF receptors as potential targets for molecular therapy in breast cancer. Curr Med Chem 2007; 14(7): 735-43.
80. Board R, Jayson GC. Platelet-derived growth factor receptor (PDGFR): a target for anticancer therapeutics. Drug Resist Updat 2005; 8(1-2): 75-83.
81. Cohen MH, Williams G, Johnson JR, et al. Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin Cancer Res 2002; 8(5): 935-42.
82. Dagher R, Cohen M, Williams G, et al. Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res 2002; 8(10): 3034-8.
83. Rubin BP, Schuetze SM, Eary JF, et al. Molecular targeting of platelet-derived growth factor B by imatinib mesylate in a patient with metastatic dermatofibrosarcoma protuberans. J Clin Oncol 2002; 20(17): 3586-91.
84. Laird AD, Vajkoczy P, Shawver LK, et al. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res 2000; 60(15): 4152-60.
85. Coleman RL, Broaddus RR, Bodurka DC, et al. Phase II trial of imatinib mesylate in patients with recurrent platinum-and taxaneresistant epithelial ovarian and primary peritoneal cancers. Gynecol Oncol 2006; 101(1): 126-31.
86. Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003; 9(1): 327-37.
87. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004; 64(19): 7099-109.
88. Roussidis AE, Mitropoulou TN, Theocharis AD, et al. STI571 as a potent inhibitor of growth and invasiveness of human epithelial breast cancer cells. Anticancer Res 2004; 24(3a): 1445-7.
89. Triozzi PL, Aldrich W, Dombos C. Differential effects of imatinib mesylate against uveal melanoma in vitro and in vivo. Melanoma Res 2008; 18(6): 420-30.
90. Gioni V, Karampinas T, Voutsinas G, et al. Imatinib mesylate inhibits proliferation and exerts an antifibrotic effect in human breast stroma fibroblasts. Mol Cancer Res 2008; 6(5): 706-14.
91. Stahtea XN, Roussidis AE, Kanakis I, et al. Imatinib inhibits colorectal cancer cell growth and suppresses stromal-induced growth stimulation, MT1-MMP expression and pro-MMP2 activation. Int J Cancer 2007; 121(12): 2808-14.
92. Kinoshita K, Nakagawa K, Hamada J, et al. Imatinib mesylate inhibits the proliferation-stimulating effect of human lung cancerassociated stromal fibroblasts on lung cancer cells Int J Oncol 2010; 37(4): 869-77.
93. Bergamaschi A, Tagliabue E, Sorlie T, et al. Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol 2008; 214: 357-67.
94. Bacac M, Provero P, Mayran N, et al. A mouse stromal response to tumor invasion predicts prostate and breast cancer patient survival. PLoS One 2006; 1: e32.