Endoglin for tumor imaging and targeted cancer therapy

Expert Opinion on Therapeutic Targets

Volumn 17, Issue 4, 2013, Pages 421-435

  Paauwe, Madelon ^a   Ten Dijke, Peter ^a   Hawinkels, Lukas JAC ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Angiogenesis; CD105; Microvessel density; TGF ; TRC105

Indexed keywords

ACTIVIN RECEPTOR LIKE KINASE 1; BEVACIZUMAB; BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN 2; CELL MARKER; CYCLOPHOSPHAMIDE; DNA VACCINE; ENDOGLIN; ENDOGLIN FC; ENDOGLIN VACCINE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INTERLEUKIN 12; MATRIX METALLOPROTEINASE 14; MJ7 18 ENDOGLIN ANTIBODY; MJ7 18 ENDOGLIN ANTIBODY I 125; NEUTRALIZING ANTIBODY; PROSTATE SPECIFIC ANTIGEN; PROTEIN ANTIBODY; RADIOPHARMACEUTICAL AGENT; TETRADECYL SULFATE SODIUM; THALIDOMIDE; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 3; TRC 105; TRC 105 CU 64; UNCLASSIFIED DRUG; ZYXIN;

ADVANCED CANCER; ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; ANTIANGIOGENIC THERAPY; ANTINEOPLASTIC ACTIVITY; AUTORADIOGRAPHY; BLOOD VESSEL PARAMETERS; BREAST CANCER; BREAST METASTASIS; CANCER DIAGNOSIS; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CARCINOMATOUS PERITONITIS; CARCINOSARCOMA; CHROMOSOME 9; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; DIAGNOSTIC IMAGING; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG TARGETING; ENDOTHELIUM CELL; EPISTAXIS; EXTRACELLULAR MATRIX; FIBROSIS; GLIOBLASTOMA; HEART MUSCLE FIBROSIS; HEMATOPOIETIC STEM CELL; HUMAN; IMAGING; IMMUNOHISTOLOGY; IN VITRO STUDY; IN VIVO STUDY; LIVER CANCER; LIVER CELL CARCINOMA; MICROBUBBLE; MICROVESSEL DENSITY; MOLECULAR IMAGING; MOLECULARLY TARGETED THERAPY; NEURAL CREST; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OVARY CARCINOMA; POSITRON EMISSION TOMOGRAPHY; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TRANSPORT; RECURRENT CANCER; RENDU OSLER WEBER DISEASE; REVIEW; SENSITIVITY AND SPECIFICITY; SIGNAL TRANSDUCTION; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; TRANSITIONAL CELL CARCINOMA; TUMOR IMAGING; TUMOR VASCULARIZATION; UTERINE CARCINOSARCOMA; UTERINE TUBE CARCINOMA; UTERUS CARCINOMA; ZONA PELLUCIDA;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTIGENS, CD; AUTOANTIBODIES; BIOLOGICAL MARKERS; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASM PROTEINS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; NEOVASCULARIZATION, PHYSIOLOGIC; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION;

EID: 84875143880     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2013.758716     Document Type: Review

References (160)

1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90
2. Folkman J, Cole P, Zimmerman S. Tumor behavior in isolated perfused organs: In vitro growth and metastases of biopsy material in rabbit thyroid and canine intestinal segment. Ann Surg 1966;164:491-502
3. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-57
4. Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible for angiogenesis. J Exp Med 1971;133:275-88
5. Prewett M, Huber J, Li Y, et al. Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res 1999;59:5209-18
6. Sitohy B, Nagy JA, Dvorak HF. Anti-VEGF/VEGFR therapy for cancer: Reassessing the target. Cancer Res 2012;72:1909-14
7. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 2008;8:592-603
8. Roberts AB, Anzano MA, Wakefield LM, et al. Type beta transforming growth factor: A bifunctional regulator of cellular growth. Proc Natl Acad Sci USA 1985;82:119-23
9. Roberts AB, Roberts AB. The dynamic roles of TGF-beta in cancer. J Pathol 2011;223:205-18
10. Massague J. TGF-beta in cancer. Cell 2008;134:215-30
11. Bernabeu C, Lopez-Novoa JM, Quintanilla M. The emerging role of TGF-beta superfamily coreceptors in cancer. Biochim Biophys Acta 2009;1792:954-73
12. Akhurst RJ, Hata A. Targeting the TGF-beta signalling pathway in disease. Nat Rev Drug Discov 2012;11:790-811
13. Burrows FJ, Derbyshire EJ, Tazzari PL, et al. Up-regulation of endoglin on vascular endothelial cells in human solid tumors: Implications for diagnosis and therapy. Clin Cancer Res 1995;1:1623-34
14. Miller DW, Graulich W, Karges B, et al. Elevated expression of endoglin, a component of the TGF-beta-receptor complex, correlates with proliferation of tumor endothelial cells. Int J Cancer 1999;81:568-72
15. Fonsatti E, Jekunen AP, Kairemo KJ, et al. Endoglin is a suitable target for efficient imaging of solid tumors: In vivo evidence in a canine mammary carcinoma model. Clin Cancer Res 2000;6:2037-43
16. Taranger-Charpin C, Dales JP, Garcia S, et al. The immunohistochemical expression of CD105 is a marker for high metastatic risk and worse prognosis in breast cancers. Bull Acad Natl Med 2003;187:1129-45
17. Zijlmans HJ, Fleuren GJ, Hazelbag S, et al. Expression of endoglin (CD105) in cervical cancer. Br J Cancer 2009;100:1617-26
18. Seon BK, Haba A, Matsuno F, et al. Endoglin-targeted cancer therapy. Curr Drug Deliv 2011;8:135-43
19. Fonsatti E, Nicolay HJ, Altomonte M, et al. Targeting cancer vasculature via endoglin/CD105: A novel antibody-based diagnostic and therapeutic strategy in solid tumours. Cardiovasc Res 2010;86:12-19
20. Dallas NA, Samuel S, Xia L, et al. Endoglin (CD105): A marker of tumor vasculature and potential target for therapy. Clin Cancer Res 2008;14:1931-7
21. Fernandez-Ruiz E, St-Jacques S, Bellon T, et al. Assignment of the human endoglin gene (END) to 9q34->qter. Cytogenet Cell Genet 1993;64:204-7
22. McAllister KA, Grogg KM, Johnson DW, et al. Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 1994; 8:345-51
23. Pece N, Vera S, Cymerman U, et al. Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative. J Clin Invest 1997;100:2568-79
24. Raab U, Velasco B, Lastres P, et al. Expression of normal and truncated forms of human endoglin. Biochem J 1999;339(Pt 3):579-88
25. Cowan PJ, Shinkel TA, Fisicaro N, et al. Targeting gene expression to endothelium in transgenic animals: A comparison of the human ICAM-2, PECAM-1 and endoglin promoters. Xenotransplantation 2003;10:223-31
26. Graulich W, Nettelbeck DM, Fischer D, et al. Cell type specificity of the human endoglin promoter. Gene 1999;227:55-62
27. Velasco B, Ramirez JR, Relloso M, et al. Vascular gene transfer driven by endoglin and ICAM-2 endothelial-specific promoters. Gene Ther 2001;8:897-904
28. Rius C, Smith JD, Almendro N, et al. Cloning of the promoter region of human endoglin, the target gene for hereditary hemorrhagic telangiectasia type 1. Blood 1998;92:4677-90
29. Gougos A, Letarte M. Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem 1990;265:8361-4
30. Ge AZ, Butcher EC. Cloning and expression of a cDNA encoding mouse endoglin, an endothelial cell TGF-beta ligand. Gene 1994;138:201-6
31. Yamashita H, Ichijo H, Grimsby S, et al. Endoglin forms a heteromeric complex with the signaling receptors for transforming growth factor-beta. J Biol Chem 1994;269:1995-2001
32. Bellon T, Corbi A, Lastres P, et al. Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions. Eur J Immunol 1993;23:2340-5
33. Gougos A, St JS, Greaves A, et al. Identification of distinct epitopes of endoglin, an RGD-containing glycoprotein of endothelial cells, leukemic cells, and syncytiotrophoblasts. Int Immunol 1992;4:83-92
34. Moren A, Ichijo H, Miyazono K. Molecular cloning and characterization of the human and porcine transforming growth factor-beta type III receptors. Biochem Biophys Res Commun 1992;189:356-62
35. Lebrin F, Goumans MJ, Jonker L, et al. Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction. EMBO J 2004;23:4018-28
36. Barbara NP, Wrana JL, Letarte M. Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily. J Biol Chem 1999;274:584-94
37. Castonguay R, Werner ED, Matthews RG, et al. Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth. J Biol Chem 2011;286:30034-46
38. Wang XF, Lin HY, Ng-Eaton E, et al. Expression cloning and characterization of the TGF-beta type III receptor. Cell 1991;67:797-805
39. Lopez-Casillas F, Cheifetz S, Doody J, et al. Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-beta receptor system. Cell 1991;67:785-95
40. Scharpfenecker M, van Dinther M, Liu Z, et al. BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis. J Cell Sci 2007;120:964-72
41. Letamendia A, Lastres P, Botella LM, et al. Role of endoglin in cellular responses to transforming growth factorbeta. A comparative study with betaglycan. J Biol Chem 1998;273:33011-19
42. Lopez-Casillas F, Wrana JL, Massague J. Betaglycan presents ligand to the TGF-beta signaling receptor. Cell 1993;73:1435-44
43. Wong SH, Hamel L, Chevalier S, Philip A. Endoglin expression on human microvascular endothelial cells association with betaglycan and formation of higher order complexes with TGF-beta signalling receptors. Eur J Biochem 2000;267:5550-60
44. Llorca O, Trujillo A, Blanco FJ, Bernabeu C. Structural model of human endoglin, a transmembrane receptor responsible for hereditary hemorrhagic telangiectasia. J Mol Biol 2007;365:694-705
45. Jovine L, Darie CC, Litscher ES, Wassarman PM. Zona pellucida domain proteins. Annu Rev Biochem 2005;74:83-114
46. Rossi E, Sanz-Rodriguez F, Eleno N, et al. Endothelial endoglin is involved in inflammation: Role in leukocyte adhesion and transmigration. Blood 2012; [Epub ahead of print]
47. Guerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C. Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II. J Biol Chem 2002;277:29197-209
48. Lastres P, Martin-Perez J, Langa C, Bernabeu C. Phosphorylation of the human-transforming-growth-factor-betabinding protein endoglin. Biochem J 1994;301(Pt 3):765-8
49. Koleva RI, Conley BA, Romero D, et al. Endoglin structure and function: Determinants of endoglin phosphorylation by transforming growth factor-beta receptors. J Biol Chem 2006;281:25110-23 8 signaling and endothelial cell migration. Carcinogenesis 2010;31:435-41
50. Sanchez-Elsner T, Botella LM, Velasco B, et al. Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-beta pathways. J Biol Chem 2002;277:43799-808
51. Li C, Guo B, Bernabeu C, Kumar S. Angiogenesis in breast cancer: The role of transforming growth factor-beta and CD105. Microsc Res Tech 2001;52:437-49
52. Hawinkels LJ, Kuiper P, Wiercinska E, et al. Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis. Cancer Res 2010;70:4141-50
53. Lastres P, Bellon T, Cabanas C, et al. Regulated expression on human macrophages of endoglin, an Arg-Gly-Asp-containing surface antigen. Eur J Immunol 1992;22:393-7
54. Mancini ML, Verdi JM, Conley BA, et al. Endoglin is required for myogenic differentiation potential of neural crest stem cells. Dev Biol 2007;308:520-33
55. Chen CZ, Li M, de GD, et al. Identification of endoglin as a functional marker that defines long-term repopulating hematopoietic stem cells. Proc Natl Acad Sci USA 2002;99:15468-73
56. Fonsatti E, Del VL, Altomonte M, et al. Endoglin: An accessory component of the TGF-beta-binding receptor-complex with diagnostic, prognostic, and bioimmunotherapeutic potential in human malignancies. J Cell Physiol 2001;188:1-7
57. St-Jacques S, Forte M, Lye SJ, Letarte M. Localization of endoglin, a transforming growth factor-beta binding protein, and of CD44 and integrins in placenta during the first trimester of pregnancy. Biol Reprod 1994;51:405-13
58. Vogel W, Grunebach F, Messam CA, et al. Heterogeneity among human bone marrow-derived mesenchymal stem cells and neural progenitor cells. Haematologica 2003;88:126-33
59. Levi B, Wan DC, Glotzbach JP, et al. CD105 protein depletion enhances human adipose-derived stromal cell osteogenesis through reduction of transforming growth factor-beta1 (TGF-beta1) signaling. J Biol Chem 2011;286:39497-509
60. Bax NA, van Oorschot AA, Maas S, et al. In vitro epithelial-to- mesenchymal transformation in human adult epicardial cells is regulated by TGF-beta-signaling and WT1. Basic Res Cardiol 2011;106:829-47
61. Chen CZ, Li L, Li M, Lodish HF. The endoglin(positive) sca-1(positive) rhodamine(low) phenotype defines a near-homogeneous population of long-term repopulating hematopoietic stem cells. Immunity 2003;19:525-33
62. Conley BA, Smith JD, Guerrero-Esteo M, et al. Endoglin, a TGF-beta receptor-associated protein, is expressed by smooth muscle cells in human atherosclerotic plaques. Atherosclerosis 2000;153:323-35
63. Bot PT, Hoefer IE, Sluijter JP, et al. Increased expression of the transforming growth factor-beta signaling pathway, endoglin, and early growth response-1 in stable plaques. Stroke 2009;40:439-47
64. van Laake LW, van den Driesche S, Post S, et al. Endoglin has a crucial role in blood cell-mediated vascular repair. Circulation 2006;114:2288-97
65. Post S, Smits AM, van den Broek AJ, et al. Impaired recruitment of HHT-1 mononuclear cells to the ischaemic heart is due to an altered CXCR4/CD26 balance. Cardiovasc Res 2010;85:494-502
66. Venkatesha S, Toporsian M, Lam C, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 2006;12:642-9
67. Pardali E, van der Schaft DW, Wiercinska E, et al. Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanoma. Oncogene 2011;30:334-45
68. Altomonte M, Montagner R, Fonsatti E, et al. Expression and structural features of endoglin (CD105), a transforming growth factor beta1 and beta3 binding protein, in human melanoma. Br J Cancer 1996;74:1586-91
69. Henriksen R, Gobl A, Wilander E, et al. Expression and prognostic significance of TGF-beta isotypes, latent TGF-beta1 binding protein, TGF-beta type I and type II receptors, and endoglin in normal ovary and ovarian neoplasms. Lab Invest 1995;73:213-20
70. Jovanovic BD, Huang S, Liu Y, et al. A simple analysis of gene expression and variability in gene arrays based on repeated observations. Am J Pharmacogenomics 2001;1:145-52
71. Craft CS, Romero D, Vary CP, Bergan RC. Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway. Oncogene 2007;26:7240-50
72. Li DY, Sorensen LK, Brooke BS, et al. Defective angiogenesis in mice lacking endoglin. Science 1999;284:1534-7
73. Arthur HM, Ure J, Smith AJ, et al. Endoglin, an ancillary TGF-beta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development. Dev Biol 2000;217:42-53
74. Bourdeau A, Dumont DJ, Letarte M. A murine model of hereditary hemorrhagic telangiectasia. J Clin Invest 1999;104:1343-51
75. ten Dijke P, Arthur HM. Extracellular control of TGF-beta signalling in vascular development and disease. Nat Rev Mol Cell Biol 2007;8:857-69
76. Bourdeau A, Faughnan ME, Letarte M. Endoglin-deficient mice, a unique model to study hereditary hemorrhagic telangiectasia. Trends Cardiovasc Med 2000;10:279-85
77. Lebrin F, Deckers M, Bertolino P, ten Dijke P. TGF-beta receptor function in the endothelium. Cardiovasc Res 2005;65:599-608
78. Pece-Barbara N, Cymerman U, Vera S, et al. Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1. Hum Mol Genet 1999;8:2171-81
79. Lebrin F, Srun S, Raymond K, et al. Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nat Med 2010;16:420-8
80. Szilagyi A, Ghali MP. Pharmacological therapy of vascular malformations of the gastrointestinal tract. Can J Gastroenterol 2006;20:171-8
81. Albinana V, Bernabeu-Herrero ME, Zarrabeitia R, et al. Estrogen therapy for hereditary haemorrhagic telangiectasia (HHT): Effects of raloxifene, on Endoglin and ALK1 expression in endothelial cells. Thromb Haemost 2010;103:525-34
82. Perez-Gomez E, Del CG, Juan FS, et al. The role of the TGF-beta coreceptor endoglin in cancer. ScientificWorld Journal 2010;10:2367-84
83. Massague J, Gomis RR. The logic of TGF-beta signaling. FEBS Lett 2006;580:2811-20
84. Holderfield MT, Hughes CC. Crosstalk between vascular endothelial growth factor, notch, and transforming growth factor-beta in vascular morphogenesis. Circ Res 2008;102:637-52
85. David L, Feige JJ, Bailly S. Emerging role of bone morphogenetic proteins in angiogenesis. Cytokine Growth Factor Rev 2009;20:203-12
86. Tian H, Mythreye K, Golzio C, et al. Endoglin mediates fibronectin/alpha5beta1 integrin and TGF-beta pathway crosstalk in endothelial cells. EMBO J 2012;31:3885-900
87. Goumans MJ, Valdimarsdottir G, Itoh S, et al. Activin receptor-like kinase (ALK) 1 is an antagonistic mediator of lateral TGF-beta/ALK5 signaling. Mol Cell 2003;12:817-28
88. Goumans MJ, Valdimarsdottir G, Itoh S, et al. Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J 2002;21:1743-53
89. ten Dijke P, Goumans MJ, Pardali E. Endoglin in angiogenesis and vascular diseases. Angiogenesis 2008;11:79-89
90. Verrecchia F, Mauviel A. Transforming growth factor-beta signaling through the Smad pathway: Role in extracellular matrix gene expression and regulation. J Invest Dermatol 2002;118:211-15
91. Kapur NK, Wilson S, Yunis AA, et al. Reduced endoglin activity limits cardiac fibrosis and improves survival in heart failure. Circulation 2012;125:2728-38
92. Zhang YE. Non-Smad pathways in TGF-beta signaling. Cell Res 2009;19:128-39
93. Lebrin F, Mummery CL. Endoglin-mediated vascular remodeling: Mechanisms underlying hereditary hemorrhagic telangiectasia. Trends Cardiovasc Med 2008;18:25-32
94. Conley BA, Koleva R, Smith JD, et al. Endoglin controls cell migration and composition of focal adhesions: Function of the cytosolic domain. J Biol Chem 2004;279:27440-9
95. Sanz-Rodriguez F, Guerrero-Esteo M, Botella LM, et al. Endoglin regulates cytoskeletal organization through binding to ZRP-1, a member of the Lim family of proteins. J Biol Chem 2004;279:32858-68
96. Lee NY, Blobe GC. The interaction of endoglin with beta-arrestin2 regulates transforming growth factor-beta-mediated ERK activation and migration in endothelial cells. J Biol Chem 2007;282:21507-17
97. Li C, Issa R, Kumar P, et al. CD105 prevents apoptosis in hypoxic endothelial cells. J Cell Sci 2003;116:2677-85
98. Leask A. TGF-beta, cardiac fibroblasts, and the fibrotic response. Cardiovasc Res 2007;74:207-12
99. Hawinkels LJ, ten Dijke P. Exploring anti-TGF-beta therapies in cancer and fibrosis. Growth Factors 2011;29:140-52
100. Maring JA, Trojanowska M, ten Dijke P. Role of endoglin in fibrosis and scleroderma. Int Rev Cell Mol Biol 2012;297:295-308
101. Obreo J, Diez-Marques L, Lamas S, et al. Endoglin expression regulates basal and TGF-beta1-induced extracellular matrix synthesis in cultured L6E9 myoblasts. Cell Physiol Biochem 2004;14:301-10
102. de Wever O, Mareel M. Role of tissue stroma in cancer cell invasion. J Pathol 2003;200:429-47
103. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor-beta1 induces alpha -smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 1993;122:103-11
104. Hawinkels LJ, Paauwe M, Verspaget HW, et al. Interaction with colon cancer cells hyperactivates TGF-beta signalling in cancer-associated fibroblasts. Oncogene 2012;In press
105. Romero D, O'Neill C, Terzic A, et al. Endoglin regulates cancer-stromal cell interactions in prostate tumors. Cancer Res 2011;71:3482-93
106. Duwel A, Eleno N, Jerkic M, et al. Reduced tumor growth and angiogenesis in endoglin-haploinsufficient mice. Tumour Biol 2007;28:1-8
107. Braghiroli MI, Sabbaga J, Hoff PM. Bevacizumab: Overview of the literature. Expert Rev Anticancer Ther 2012;12:567-80
108. Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 2011;10:417-27
109. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335-42
110. Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 1991;324:1-8
111. Kumar S, Ghellal A, Li C, et al. Breast carcinoma: Vascular density determined using CD105 antibody correlates with tumor prognosis. Cancer Res 1999;59:856-61
112. Dales JP, Garcia S, Carpentier S, et al. Long-term prognostic significance of neoangiogenesis in breast carcinomas: Comparison of Tie-2/Tek, CD105, and CD31 immunocytochemical expression. Hum Pathol 2004;35:176-83
113. Beketic-Oreskovic L, Ozretic P, Rabbani ZN, et al. Prognostic significance of carbonic anhydrase IX (CA-IX), endoglin (CD105) and 8-hydroxy-2¢-deoxyguanosine (8-OHdG) in breast cancer patients. Pathol Oncol Res 2011;17:593-603
114. Erdem O, Taskiran C, Onan MA, et al. CD105 expression is an independent predictor of survival in patients with endometrial cancer. Gynecol Oncol 2006;103:1007-11
115. Brewer CA, Setterdahl JJ, Li MJ, et al. Endoglin expression as a measure of microvessel density in cervical cancer. Obstet Gynecol 2000;96:224-8
116. Taskiran C, Erdem O, Onan A, et al. The prognostic value of endoglin (CD105) expression in ovarian carcinoma. Int J Gynecol Cancer 2006;16:1789-93
117. Eshghyar N, Mohammadi N, Rahrotaban S, et al. Endoglin (CD105) positive microvessel density and its relationship with lymph node metastasis in squamous cell carcinoma of the tongue. Arch Iran Med 2011;14:276-80
118. Li SL, Gao DL, Zhao ZH, et al. Correlation of matrix metalloproteinase suppressor genes RECK, VEGF, and CD105 with angiogenesis and biological behavior in esophageal squamous cell carcinoma. World J Gastroenterol 2007;13:6076-81
119. Chuang HC, Su CY, Huang HY, et al. High expression of CD105 as a prognostic predictor of early tongue cancer. Laryngoscope 2006;116:1175-9
120. Martone T, Rosso P, Albera R, et al. Prognostic relevance of CD105+ microvessel density in HNSCC patient outcome. Oral Oncol 2005;41:147-55
121. Marioni G, Marino F, Blandamura S, et al. Neoangiogenesis in laryngeal carcinoma: Angiogenin and CD105 expression is related to carcinoma recurrence rate and disease-free survival. Histopathology 2010;57:535-43
122. Saad RS, Liu YL, Nathan G, et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol 2004;17:197-203
123. Akagi K, Ikeda Y, Sumiyoshi Y, et al. Estimation of angiogenesis with anti-CD105 immunostaining in the process of colorectal cancer development. Surgery 2002;131:S109-13
124. Tanaka F, Otake Y, Yanagihara K, et al. Correlation between apoptotic index and angiogenesis in non-small cell lung cancer: Comparison between CD105 and CD34 as a marker of angiogenesis. Lung Cancer 2003;39:289-96
125. Yang LY, Lu WQ, Huang GW, Wang W. Correlation between CD105 expression and postoperative recurrence and metastasis of hepatocellular carcinoma. BMC Cancer 2006;6:110
126. Wikstrom P, Lissbrant IF, Stattin P, et al. Endoglin (CD105) is expressed on immature blood vessels and is a marker for survival in prostate cancer. Prostate 2002;51:268-75
127. Lin H, Huang CC, Ou YC, et al. High immunohistochemical expression of TGF-beta1 predicts a poor prognosis in cervical cancer patients who harbor enriched endoglin microvessel density. Int J Gynecol Pathol 2012;31:482-9
128. Perez-Gomez E, Villa-Morales M, Santos J, et al. A role for endoglin as a suppressor of malignancy during mouse skin carcinogenesis. Cancer Res 2007;67:10268-77
129. Levine RJ, Lam C, Qian C, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med 2006;355:992-1005
130. Li C, Guo B, Wilson PB, et al. Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer. Int J Cancer 2000;89:122-6
131. Takahashi N, Kawanishi-Tabata R, Haba A, et al. Association of serum endoglin with metastasis in patients with colorectal, breast, and other solid tumors, and suppressive effect of chemotherapy on the serum endoglin. Clin Cancer Res 2001;7:524-32
132. Furstenberger G, von Moos R, Lucas R, et al. Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer. Br J Cancer 2006;94:524-31
133. Mysliwiec P, Pawlak K, Bandurski R, Kedra B. Soluble angiogenesis markers in gastric tumor patients. Folia Histochem Cytobiol 2009;47:81-6
134. Mysliwiec P, Pawlak K, Kuklinski A, Kedra B. Combined perioperative plasma endoglin and VEGF-A assessment in colorectal cancer patients. Folia Histochem Cytobiol 2008;46:487-92
135. Bellone G, Solerio D, Chiusa L, et al. Transforming growth factor-beta binding receptor endoglin (CD105) expression in esophageal cancer and in adjacent nontumorous esophagus as prognostic predictor of recurrence. Ann Surg Oncol 2007;14:3232-42
136. Yagmur E, Rizk M, Stanzel S, et al. Elevation of endoglin (CD105) concentrations in serum of patients with liver cirrhosis and carcinoma. Eur J Gastroenterol Hepatol 2007;19:755-61
137. Karam JA, Svatek RS, Karakiewicz PI, et al. Use of preoperative plasma endoglin for prediction of lymph node metastasis in patients with clinically localized prostate cancer. Clin Cancer Res 2008;14:1418-22
138. Svatek RS, Karam JA, Roehrborn CG, et al. Preoperative plasma endoglin levels predict biochemical progression after radical prostatectomy. Clin Cancer Res 2008;14:3362-6
139. Fujita K, Ewing CM, Chan DY, et al. Endoglin (CD105) as a urinary and serum marker of prostate cancer. Int J Cancer 2009;124:664-9
140. Passe TJ, Bluemke DA, Siegelman SS. Tumor angiogenesis: Tutorial on implications for imaging. Radiology 1997;203:593-600
141. Korpanty G, Carbon JG, Grayburn PA, et al. Monitoring response to anticancer therapy by targeting microbubbles to tumor vasculature. Clin Cancer Res 2007;13:323-30
142. Zhang Y, Yang Y, Hong H, Cai W. Multimodality molecular imaging of CD105 (Endoglin) expression. Int J Clin Exp Med 2011;4:32-42
143. Dassler K, Roohi F, Lohrke J, et al. Current limitations of molecular magnetic resonance imaging for tumors as evaluated with high-relaxivity CD105-specific iron oxide nanoparticles. Invest Radiol 2012;47:383-91
144. Bredow S, Lewin M, Hofmann B, et al. Imaging of tumour neovasculature by targeting the TGF-beta binding receptor endoglin. Eur J Cancer 2000;36:675-81
145. Costello B, Li C, Duff S, et al. Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target. Int J Cancer 2004;109:436-41
146. Hong H, Zhang Y, Engle JW, et al. In vivo targeting and positron emission tomography imaging of tumor vasculature with (66)Ga-labeled nano-graphene. Biomaterials 2012;33:4147-56
147. Zhang Y, Hong H, Engle JW, et al. Positron emission tomography and optical imaging of tumor CD105 expression with a dual-labeled monoclonal antibody. Mol Pharm 2012;9:645-53
148. Reisfeld RA, Niethammer AG, Luo Y, Xiang R. DNA vaccines suppress tumor growth and metastases by the induction of anti-angiogenesis. Immunol Rev 2004;199:181-90
149. Tan GH, Tian L, Wei YQ, et al. Combination of low-dose cisplatin and recombinant xenogeneic endoglin as a vaccine induces synergistic antitumor activities. Int J Cancer 2004;112:701-6
150. Wood LM, Pan ZK, Guirnalda P, et al. Targeting tumor vasculature with novel Listeria-based vaccines directed against CD105. Cancer Immunol Immunother 2011;60:931-42
151. Jarosz M, Jazowiecka-Rakus J, Cichon T, et al. Therapeutic antitumor potential of endoglin-based DNA vaccine combined with immunomodulatory agents. Gene Ther 2012;In press
152. Seon BK, Matsuno F, Haruta Y, et al. Long-lasting complete inhibition of human solid tumors in SCID mice by targeting endothelial cells of tumor vasculature with antihuman endoglin immunotoxin. Clin Cancer Res 1997;3:1031-44
153. Takahashi N, Haba A, Matsuno F, Seon BK. Antiangiogenic therapy of established tumors in human skin/severe combined immunodeficiency mouse chimeras by anti-endoglin (CD105) monoclonal antibodies, and synergy between anti-endoglin antibody and cyclophosphamide. Cancer Res 2001;61:7846-54
154. Uneda S, Toi H, Tsujie T, et al. Anti-endoglin monoclonal antibodies are effective for suppressing metastasis and the primary tumors by targeting tumor vasculature. Int J Cancer 2009;125:1446-53
155. Tsujie M, Tsujie T, Toi H, et al. Anti-tumor activity of an anti-endoglin monoclonal antibody is enhanced in immunocompetent mice. Int J Cancer 2008;122:2266-73
156. Rosen LS, Hurwitz HI, Wong MK, et al. A Phase I first-in-human study of TRC105 (Anti-Endoglin Antibody) in patients with advanced cancer. Clin Cancer Res 2012;18:4820-9
157. www.ClinicalTrials.gov, 2012
158. Bockhorn M, Tsuzuki Y, Xu L, et al. Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts. Clin Cancer Res 2003;9:4221-6
159. Cirri P, Chiarugi P. Cancer associated fibroblasts: The dark side of the coin. Am J Cancer Res 2011;1:482-97
160. Karagiannis GS, Poutahidis T, Erdman SE, et al. Cancer-Associated Fibroblasts Drive the Progression of Metastasis through both Paracrine and Mechanical Pressure on Cancer Tissue. Mol Cancer Res 2012;10:1403-18