Skip to main content
SpringerLink
Log in

Endoglin (CD105): A Strong Candidate for Immunologic Targeting of Tumor Neovasculature in Human Malignancies

  • Chapter
Transforming Growth Factor-β in Cancer Therapy, Volume I

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 1598 Accesses

Abstract

Tumor-associated angiogenesis is a well-acknowledged therapeutic target for human malignancies, and different markers of tumor neovasculature are actively investigated as potential candidates for antiangiogenetic therapy in cancer. Among these is endoglin (CD105), a homodimeric transmembrane glycoprotein overexpressed on proliferating endothelial cells, which has been identified as a functional component of the transforming growth factor-β (TGF-β) receptor system about a decade ago. The large body of experimental data accumulated so far indicates that CD105 plays a crucial role in angiogenesis and vascular integrity; furthermore, intratumoral microvessel density as evaluated by staining for CD105 represents a strong prognostic factor in solid malignancies of different histology. In this work, we review the biologic features of CD105 and the complex of evidences highlighting its great potentialities as novel target for diagnostic and therapeutic approaches in human malignancies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005;438:932–936.

    Article  CAS  PubMed  Google Scholar 

  2. Neri D, Bicknell R. Tumour vascular targeting. Nat Rev Cancer 2005;5:436–446.

    Article  CAS  PubMed  Google Scholar 

  3. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182–1186.

    CAS  PubMed  Google Scholar 

  4. Denekamp J. Vascular endothelium as the vulnerable element in tumours. Acta Radiol Oncol 1984;23:217–225.

    Article  CAS  PubMed  Google Scholar 

  5. Burrows FJ, Thorpe PE. Eradication of large solid tumors in mice with an immunotoxin directed against tumor vasculature. Proc Natl Acad Sci USA 1993;90:8996–9000.

    Article  CAS  PubMed  Google Scholar 

  6. Haruta Y, Seon BK. Distinct human leukemia-associated cell surface glycoprotein GP160 defined by monoclonal antibody SN6. Proc Natl Acad Sci USA 1986;83:7898–7902.

    Article  CAS  PubMed  Google Scholar 

  7. Gougos A, Letarte M. Identification of a human endothelial cell antigen with monoclonal antibody 44G4 produced against a pre-B leukemic cell line. J Immunol 1988;141:1925–1933.

    CAS  PubMed  Google Scholar 

  8. 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;1:1623–1634.

    CAS  PubMed  Google Scholar 

  9. Letarte M, Greaves A, Vera S. CD105 (endoglin) cluster report. In: White Cell Differentiation Antigens. Schlossman SF, et al. Oxford, New York, Tokyo: Oxford University Press 1995:1756–1759.

    Google Scholar 

  10. Gougos A, Letarte M. Biochemical characterization of the 44G4 antigen from the HOON pre-B leukemic cell line. J Immunol 1988;141:1934–1940.

    CAS  PubMed  Google Scholar 

  11. Bellon T, Corbi A, Lastres P, Cales C, 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;23:2340–2345.

    Article  CAS  PubMed  Google Scholar 

  12. Perez-Gomez E, Eleno N, Lopez-Novoa JM, et al. Characterization of murine S-endoglin isoform and its effects on tumor development. Oncogene 2005;24:4450–4461.

    Article  CAS  PubMed  Google Scholar 

  13. Li C, Hampson IN, Hampson L, Kumar P, Bernabeu C, Kumar S. CD105 antagonizes the inhibitory signaling of transforming growth factor betal on human vascular endothelial cells. FASEB J 2000; 14:55–64.

    CAS  PubMed  Google Scholar 

  14. Duff SE, Li C, Garland JM, Kumar S. CD105 is important for angiogenesis: evidence and potential applications. FASEB J 2003;17:984–992.

    Article  CAS  PubMed  Google Scholar 

  15. Lastres P, Martin-Perez J, Langa C, Bernabeu C. Phosphorylation of the human-transforming-growth-factor-beta-binding protein endoglin. Biochem J 1994;301:765–768.

    CAS  PubMed  Google Scholar 

  16. Gougos A, Letarte M. Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem 1990;265:8361–8364.

    CAS  PubMed  Google Scholar 

  17. Ge AZ, Butcher EC. Cloning and expression of a cDNA encoding mouse endoglin, an endothelial cell TGF-beta ligand, Gene 1994;138:201–206.

    Article  CAS  PubMed  Google Scholar 

  18. Yamashita H, Ichijo H, Grimsby S, Moren A, en Dijke P, Miyazono K. Endoglin forms a heteromeric complex with the signaling receptors for transforming growth factor-beta. J Biol Chem 1994; 269:1995–2001.

    CAS  PubMed  Google Scholar 

  19. Fernandez-Ruiz E, St-Jacques S, Bellon T, Letarte M, Bernabeu C. Assignment of the human endoglin gene (END) to 9q34→qter. Cytogenet Cell Genet 1993;64:204–207.

    Article  CAS  PubMed  Google Scholar 

  20. McAllister KA, Baldwin MA, Thukkani AK, et al. Six novel mutations in the endoglin gene in hereditary hemorrhagic telangiectasia type 1 suggest a dominant-negative effect of receptor function. Hum Mol Genet 1995;4:1983–1985.

    Article  CAS  PubMed  Google Scholar 

  21. 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;8:345–351.

    Article  CAS  PubMed  Google Scholar 

  22. Pece N, Vera S, Cymerman U, White RI Jr, Wrana JL, Letarte M. Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative. J Clin Invest 1997;100:2568–2579.

    Article  CAS  PubMed  Google Scholar 

  23. van den Driesche S, Mummery CL, Westermann CJ. Hereditary hemorrhagic telangiectasia: an update on transforming growth factor beta signaling in vasculogenesis and angiogenesis. Cardiovasc Res 2003;58:20–31.

    Article  PubMed  CAS  Google Scholar 

  24. Pece-Barbara N, Cymerman U, Vera S, Marchuk DA, Letarte M. Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1. Hum Mol Genet 1999;8:2171–2181.

    Article  CAS  PubMed  Google Scholar 

  25. Paquet ME, Pece-Barbara N, Vera S, et al. Analysis of several endoglin mutants reveals no endogenous mature or secreted protein capable of interfering with normal endoglin function. Hum Mol Genet 2001;10:1347–1357.

    Article  CAS  PubMed  Google Scholar 

  26. Bourdeau A, Dumont DJ, Letarte M. A murine model of hereditary hemorrhagic telangiectasia. J Clin Invest 1999;104:1343–1351.

    Article  CAS  PubMed  Google Scholar 

  27. Bourdeau A, Faughman ME, McDonald ML, Paterson AD, Wanless IR, Letarte M. Potential role of modifier genes influencing transforming growth factor-beta1 levels in the development of vascular defects in endoglin heterozygous mice with hereditary hemorrhagic telangiectasia. Am J Pathol 2001; 158:2011–2020.

    CAS  PubMed  Google Scholar 

  28. Fernandez-L A, Sanz-Rodriguez F, Zarrabeitia R, et al. Blood outgrowth endothelial cells from Hereditary Haemorrhagic Telangiectasia patients reveal abnormalities compatible with vascular lesions. Cardiovasc Res 2005;68:235–248.

    Article  CAS  Google Scholar 

  29. Goldschmidt N, Metzger S, Wexler ID, Goldshmidt O, Hershcovici T, Chajek-Shaul T. Association of hereditary hemorrhagic telangiectasia and hereditary nonpolyposis colorectal cancer in the same kindred. Int J Cancer 2005;116:808–812.

    Article  CAS  PubMed  Google Scholar 

  30. Cheifetz S, Bellon T, Cales C, et al. Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem 1992;267:19,027–19,030.

    CAS  PubMed  Google Scholar 

  31. 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;274:584–594.

    Article  CAS  PubMed  Google Scholar 

  32. Letamendia A, Lastres P, Botella LM, et al. Role of endoglin in cellular responses to transforming growth factor-beta. A comparative study with betaglycan. J Biol Chem 1998;273:33,011–33,019.

    Article  CAS  PubMed  Google Scholar 

  33. Guerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C. Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receports I and II. J Biol Chem 2002;277:29,197–29,209.

    Article  CAS  PubMed  Google Scholar 

  34. Govinden R, Bhoola KD. Genealogy, expression, and cellular function of transforming growth factor-beta. Pharmacol Ther 2003;98:257–265.

    Article  CAS  PubMed  Google Scholar 

  35. Lebrin F, Deckers M, Bertolino P, ten Dijke P. TGF-beta receptor function in the endothelium. Cardiovasc Res 2005;65:599–608.

    Article  CAS  PubMed  Google Scholar 

  36. Goumans MJ, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P, ten Dijke P. Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J 2002;21:1743–1753.

    Article  CAS  PubMed  Google Scholar 

  37. Lebrin F, Goumans MJ, Jonker L, et al. Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction. EMBO J 2004;23:4018–4028.

    Article  CAS  PubMed  Google Scholar 

  38. Blanco FJ, Santibanez JF, Guerrero-Esteo M, Langa C, Vary CP, Bernabeu C. Interaction and functional interplay between endoglin and ALK-1, two components of the endothelial transorming growth factor-beta receptor complex. J Cell Physiol 2005;204:574–584.

    Article  CAS  PubMed  Google Scholar 

  39. Guo B, Slevin M, Li C, et al. CD105 inhibits transforming growth factor-beta-Smad3 signalling. Anticancer Res 2004;24:1337–1345.

    CAS  PubMed  Google Scholar 

  40. Pece-Barbara N, Vera S, Kathirkamathamby K, et al. Endoglin null endothelial cells proliferate faster and are more responsive to transforming growth factor beta1 with higher affinity receptors and an activated Alk1 pathway. J Biol Chem 2005;280:27,800–27,808.

    Article  CAS  PubMed  Google Scholar 

  41. Lastres P, Letamendia A, Zhang H, et al. Endoglin modulates cellular responses to TGF-beta 1. J Cell Biol 1996;133:1109–1121.

    Article  CAS  PubMed  Google Scholar 

  42. Ma X, Labinaz M, Goldstein J, et al. Endoglin is overexpressed after arterial injury and is required for transforming growth factor-beta-induced inhibition of smooth muscle cell migration. Arterioscler Thromb Vasc Biol 2000;20:2546–2552.

    CAS  PubMed  Google Scholar 

  43. She X, Matsuno F, Harada N, Tsai H, Seon BK. Synergy between anti-endoglin (CD105) monoclonal antibodies and TGF-beta in suppression of growth of human endothelial cells. Int J Cancer 2004; 108:251–257.

    Article  CAS  PubMed  Google Scholar 

  44. Guerrero-Esteo M, Lastres P, Letamendia A, et al. Endoglin overexpression modulates cellular morphology, migration, and adhesion of mouse fibroblasts. Eur J Cell Biol 1999;78:614–623.

    CAS  PubMed  Google Scholar 

  45. Diez-Marques L, Ortega-Velazquez R, Langa C, et al. Expression of endoglin in human mesangial cells: modulation of extracellular matrix synthesis. Biochim Biophys Acta 2002;1587:36–44.

    CAS  PubMed  Google Scholar 

  46. Botella LM, Sanz-Rodriguez F, Sanchez-Elsner T, et al. Lumican is down-regulated in cells expressing endoglin. Evidence for an inverse correlationship between Endoglin and Lumican expression. Matrix Biol 2004;22:561–572.

    Article  CAS  PubMed  Google Scholar 

  47. Fonsatti E, Maio M. Highlights on endoglin (CD105): from basic findings towards clinical applications in human cancer. J Transl Med 2004;2:18.

    Article  PubMed  Google Scholar 

  48. 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;267:5550–5560.

    Article  CAS  PubMed  Google Scholar 

  49. Graulich W, Nettelbeck DM, Fischer D, Kissel T, Muller R. Cell type specificity of the human endoglin promoter. Gene 1999;227:55–62.

    Article  CAS  PubMed  Google Scholar 

  50. 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.

    Article  CAS  PubMed  Google Scholar 

  51. 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;10:223–231.

    Article  PubMed  Google Scholar 

  52. Qu R, Silver MM, Letarte M. Distribution of endoglin in early human development reveals high levels on endocardial cushion tissue mesenchyme during valve formation. Cell Tissue Res 1998;292:333–343.

    Article  CAS  PubMed  Google Scholar 

  53. Jonker L, Arthur HM. Endoglin expression in early development is associated with vasculogenesis and angiogenesis. Mech Dev 2002;110:193–196.

    Article  CAS  PubMed  Google Scholar 

  54. 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: 2037–2043.

    CAS  PubMed  Google Scholar 

  55. 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;81:568–572.

    Article  CAS  PubMed  Google Scholar 

  56. Schimming R, Marme D. Endoglin (CD105) expression in squamous cell carcinoma of the oral cavity. Head Neck 2002;24:151–156.

    Article  PubMed  Google Scholar 

  57. Fonsatti E, Del Vecchio L, Altomonte M, et al. Endoglin: An accessory component of the TGF-betabinding receptor-complex with diagnostic, prognostic, and bioimmunotherapeutic potential in human malignancies. J Cell Physiol 2001;188:1–7.

    Article  CAS  PubMed  Google Scholar 

  58. Wang JM, Kumar S, Pye D, van Agthoven AJ, Krupinski J, Hunter RD. A monoclonal antibody detects heterogeneity in vascular endothelium of tumours and normal tissues. Int J Cancer 1993;54: 363–370.

    Article  CAS  PubMed  Google Scholar 

  59. Wang JM, Kumar S, Pye D, Haboubi N, al-Nakib L. Breast carcinoma: comparative study of tumor vasculature using two endothelial cell markers. J Natl Cancer Inst 1994;86:386–388.

    Article  CAS  PubMed  Google Scholar 

  60. Wikstrom P, Lissbrant IF, Stattin P, Egevad L, Bergh A. Endoglin (CD105) is expressed on immature blood vessels and is a marker for survival in prostate cancer. Prostate 2002;51:268–275.

    Article  CAS  PubMed  Google Scholar 

  61. Bredow S, Lewin M, Hofmann B, Marecos E, Weissleder R. Imaging of tumour neovasculature by targeting the TGF-beta binding receptor endoglin. Eur J Cancer 2000;36:675–681.

    Article  CAS  PubMed  Google Scholar 

  62. Balza E, Castellani P, Zijlstra A, Neri D, Zardi L, Siri A. Lack of specificity of endoglin expression for tumor blood vessels. Int J Cancer 2001;94:579–585.

    Article  CAS  PubMed  Google Scholar 

  63. Seon BK. Expression of endoglin (CD105) in tumor blood vessels. Int J Cancer 2002;99:310–311.

    Article  CAS  PubMed  Google Scholar 

  64. Nagatsuka H, Hibi K, Gunduz M, et al. Various immunostaining patterns of CD31, CD34 and endoglin and their relationship with lymph node metastasis in oral squamous cell, carcinomas. J Oral Pathol Med 2005;34:70–76.

    Article  PubMed  Google Scholar 

  65. Fonsatti E, Altomonte M, Nicotra MR, Natali PG, Maio M. Endoglin (CD105): a powerful therapeutic target on tumor-associated angiogenetic blood vessels. Oncogene 2003;22:6557–6563.

    Article  CAS  PubMed  Google Scholar 

  66. 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;74:1586–1591.

    CAS  PubMed  Google Scholar 

  67. Postiglione L, Di Domenico G, Caraglia M, et al. Differential expression and cytoplasm/membrane distribution of endoglin (CD105) in human tumour cell lines: Implications in the modulation of cell proliferation. Int J Oncol 2005;26:1193–1201.

    CAS  PubMed  Google Scholar 

  68. Liu Y, Jovanovic B, Pins M, Lee C, Bergan RC. Over expression of endoglin in human prostate cancer suppresses cell detachment, migration and invasion. Oncogene 2002;21:8272–8281.

    Article  CAS  PubMed  Google Scholar 

  69. Jovanovic BD, Huang S, Liu Y, Naguib KN, Bergan RC. A simple analysis of gene expression and variability in gene arrays based on repeated observations. Am J Pharmacogenomics 2001;1: 145–152.

    Article  CAS  PubMed  Google Scholar 

  70. Quintanilla M, Ramirez JR, Perez-Gomez E, et al. Expression of the TGF-beta coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis. Oncogene 2003;22:5976–5985.

    Article  CAS  PubMed  Google Scholar 

  71. Cui W, Fowlis DJ, Bryson S, et al. TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 1996;86:531–542.

    Article  CAS  PubMed  Google Scholar 

  72. Letamendia A, Lastres P, Almendro N, et al. Endoglin, a component of the TGF-beta receptor system, is a differentiation marker of human choriocarcinoma cells. Int J Cancer 1998;76:541–546.

    Article  CAS  PubMed  Google Scholar 

  73. Lo Pardo C, Altomonte M, Boccuni P, et al. CD105 Workshop: Expression of CD105 on acute leucemia blast cells: application for minimal residual disease detection. In: Kishimoto T, Kikutani H, Kr von dem Borne AEG, Goyert SM, Mason DY, Miyasaka M, Moretta L, Okumura K, Shaw S Springer TA, Sugamura K, Zola H. eds, Leucocyte typing VI White Cell Differentiation Antigens. New York, London: Garland Publishing, Inc 1997:711–712.

    Google Scholar 

  74. O’Connell PJ, McKenzie A, Fisicaro N, Rockman SP, Pearse MJ, d’Apice AJ. Endoglin: a 180-kD endothelial cell and macrophage restricted differentiation molecule. Clin Exp Immunol 1992; 90:154–159.

    Article  PubMed  Google Scholar 

  75. Rokhlin OW, Cohen MB, Kubagawa H, Letarte M, Cooper MD. Differential expression of endoglin on fetal and adult hematopoietic cells in human bone marrow. J Immunol 1995;154:4456–4465.

    CAS  PubMed  Google Scholar 

  76. Sanchez-Elsner T, Botella LM, Velasco B, Langa C, Bernabeu C. Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-beta pathways. J Biol Chem 2002;277:43,799–43,808.

    Article  CAS  PubMed  Google Scholar 

  77. Zhu Y Sun Y, Xie L, Jin K, Sheibani N, Greenberg DA. Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvascular endothelial cells. Stroke 2003;34:2483–2488.

    Article  CAS  PubMed  Google Scholar 

  78. Li C, Issa R, Kumar P, Hampson IN, Lopez-Novoa JM, Bernabeu C, Kumar S. CD105 prevents apoptosis in hypoxic endothelial cells. J Cell Sci 2003;116:2677–2685.

    Article  CAS  PubMed  Google Scholar 

  79. Guo B, Kumar S, Li C, Slevin M, Kumar P. CD105 (endoglin), apoptosis, and stroke. Stroke 2004;35:94–95.

    Article  Google Scholar 

  80. Tanaka F, Ishikawa S, Yanagihara K, et al. Expression of angiopoietins and its clinical significance in non-small cell lung cancer. Cancer Res 2002;62:7124–7129.

    CAS  PubMed  Google Scholar 

  81. 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;92:4677–4690.

    CAS  PubMed  Google Scholar 

  82. Botella LM, Sanchez-Elsner T, Rius C, Corbi A, Bernabeu C. Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation. J Biol Chem 2001;276:34,486–34,494.

    Article  CAS  PubMed  Google Scholar 

  83. Ota T, Fujii M, Sugizaki T, et al. Targets of transcriptional regulation by two distinct type I receptors for transforming growth factor-beta in human umbilical vein endothelial cells. J Cell Physiol 2002;193:299–318.

    Article  CAS  PubMed  Google Scholar 

  84. Li C, Guo B, Ding S, Rius C, Langa C, Kumar P, Bernabeu C, Kumar S. TNF alpha down-regulates CD105 expression in vascular endothelial cells: a comparative study with TGF beta1. Anticancer Res 2003;23:1189–1196.

    CAS  PubMed  Google Scholar 

  85. Tang H, Low B, Rutherford SA, Hao Q. Thrombin induces endocytosis of endoglin and type-II TGF-beta receptor and down-regulation of TGF-beta signaling in endothelial cells. Blood 2005; 105:1977–1985.

    Article  CAS  PubMed  Google Scholar 

  86. Li DY, Sorensen LK, Brooke BS, et al. Defective angiogenesis in mice lacking endoglin. Science 1999;284:1534–1537.

    Article  CAS  PubMed  Google Scholar 

  87. Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ. Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 1995; 121:1845–1854.

    CAS  PubMed  Google Scholar 

  88. Goumans MJ, Zwijsen A, van Rooijen MA, Huylebroeck D, Roelen BA, Mummery CL. Transforming growth factor-beta signalling in extraembryonic mesoderm is required for yolk sac vasculogenesis in mice. Development 1999;126:3473–3483.

    CAS  PubMed  Google Scholar 

  89. Urness LD, Sorensen LK, Li DY. Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nat Genet 2000;26:328–331.

    Article  CAS  PubMed  Google Scholar 

  90. Jerkic M, Rivas-Elena JV, Prieto M, et al. Endoglin regulates nitric oxide-dependent vasodilation. FASEB J 2004;18:609–611.

    CAS  PubMed  Google Scholar 

  91. Toporsian M, Gros R, Kabir MG, et al. A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia. Circ Res 2005;96:684–692.

    Article  CAS  PubMed  Google Scholar 

  92. 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;39:289–296.

    Article  PubMed  Google Scholar 

  93. Brewer CA, Setterdahl JJ, Li MJ, Johnston JM, Mann JL, McAsey ME. Endoglin expression as a measure of microvessel density in cervical cancer. Obstet Gynecol 2000;96:224–228.

    Article  CAS  PubMed  Google Scholar 

  94. Saad RS, Jasnosz KM, Tung MY, Silverman JF. Endoglin (CD105) expression in endometrial carcinoma. Int J Gynecol Pathol 2003;22:248–253.

    Article  PubMed  Google Scholar 

  95. Martone T, Rosso P, albera R, et al. Prognostic relevance of CD105+ microvessel density in HNSCC patient outcome. Oral Oncol 2005;41:147–155.

    Article  CAS  PubMed  Google Scholar 

  96. Ho JW, Poon RT, Sun CK, Xue WC, Fan ST. Clinicopathological and prognostic implications of endoglin (CD105) expression in hepatocellular carcinoma and its adjacent non-tumorous liver. World J Gastroenterol 2005;11:176–181.

    CAS  PubMed  Google Scholar 

  97. Gomez-Esquer F, Agudo D, Martinez-Arribas F, Nunez-Villar MJ, Schneider J. mRNA expression of the angiogenesis markers VEGF and CD105 (endoglin) in human breast cancer. Anticancer Res 2004;24:1581–1585.

    CAS  PubMed  Google Scholar 

  98. Akagi K, Ikeda Y, Sumiyoshi Y, et al. Estimation of angiogenesis with anti-CD105 immunostaining in the process of colorectal cancer development. Surgery 2002;31:S109–S113.

    Article  Google Scholar 

  99. Pruneri G, Ponzoni M, Ferreri AJ, et al. Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients. Br J Haematol 2002;118:817–820.

    Article  PubMed  Google Scholar 

  100. Pruneri G, Bertolini F, Baldini L, et al. Angiogenesis occurs in hairy cell leukaemia (HCL) and in NOD/SCID mice transplanted with the HCL line Bonna-12. Br J Haematol 2003;120:695–698.

    Article  PubMed  Google Scholar 

  101. 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;7:524–532.

    CAS  PubMed  Google Scholar 

  102. Li C, Gardy R, Seon BK, et al. Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer 2003;88:1424–1431.

    Article  CAS  PubMed  Google Scholar 

  103. Calabrò L, Fonsatti E, Bellomo G, et al. Differential levels of soluble endoglin (CD105) in myeloid malignancies. J Cell Physiol 2003;194:171–175.

    Article  PubMed  CAS  Google Scholar 

  104. Maier JA, Delia D, Thorpe PE, Gasparini G. In vitro inhibition of endothelial cell growth by the antiangiogenic drug AGM-1470 (TNP-470) and the anti-endoglin antibody TEC-11. Anticancer Drugs 1997;8:238–244.

    Article  CAS  PubMed  Google Scholar 

  105. Nettelbeck DM, Miller DW, Jerome V, et al. Tarteting of adenovirus to endothelial cells by a bispecific single-chain diabody directed against the adenovirus fiber knob domain and human endoglin (CD105). Mol Ther 2001;3:882–891.

    Article  CAS  PubMed  Google Scholar 

  106. Korn T, Muller R, Kontermann RE. Bispecific single-chain diabody-mediated killing of endoglin-positive endothelial cells by cytotoxic T lymphocytes. J Immunother 2004;27:99–106.

    Article  CAS  PubMed  Google Scholar 

  107. Volkel T, Holig P, Merdan T, Muller R, Kontermann RE. Targeting of immunoliposomes to endothelial cells using a single-chain Fv fragment directed against human endoglin (CD105). Biochim Biophys Acta 2004;1663:158–166.

    Article  PubMed  CAS  Google Scholar 

  108. Savontaus MJ, Sauter BV, Huang TG, Woo SL. Transcriptional targeting of conditionally replicating adenovirus to dividing endothelial cells. Gene Ther 2002;9:972–979.

    Article  CAS  PubMed  Google Scholar 

  109. Korpanty G, Grayburn PA, Shohet RV, Brekken RA. Targeting vascular endothelium with avidin microbubbles. Ultrasound Med Biol 2005;31:1279–1283.

    Article  PubMed  Google Scholar 

  110. 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: 436–441.

    Article  CAS  PubMed  Google Scholar 

  111. Seon BK, Matsuno F, Haruta Y, Kondo M, Barcos M. 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;3:1031–1044.

    CAS  PubMed  Google Scholar 

  112. Matsuno F, Haruta Y, Kondo M, Tsai H, Barcos M, Seon BK. Induction of lasting complete regression of preformed distinct solid tumors by targeting the tumor vasculature using two new anti-endoglin monoclonal antibodies. Clin Cancer Res 1999;5:371–382.

    CAS  PubMed  Google Scholar 

  113. Tabata M, Kondo M, Haruta Y, Seon BK. Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using (125)I-labeled anti-endoglin monoclonal antibodies. Int J Cancer 1999;82:737–742.

    Article  CAS  PubMed  Google Scholar 

  114. 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: 7846–7854.

    CAS  PubMed  Google Scholar 

  115. Shiozaki K, Harada N, Greco WR, et al. Antiangiogenic chimeric anti-endoglin (CD105) antibody: pharmacokinetics and immunogenicity in nonhuman primates and effects of doxorubicin. Cancer Immunol Immunother 2006;55:140–50.

    Article  CAS  PubMed  Google Scholar 

  116. Tan GH, Wei YQ, Tian L, et al. Active immunotherapy of tumors with a recombinant xenogeneic endoglin as a model antigen. Eur J Immunol 2004;34:2012–2021.

    Article  CAS  PubMed  Google Scholar 

  117. 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: 701–706.

    Article  CAS  PubMed  Google Scholar 

  118. Kumar S, Ghellal A, Li C, et al. Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis. Cancer Res 1999;59:856–861.

    CAS  PubMed  Google Scholar 

  119. 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;35:176–183.

    Article  CAS  PubMed  Google Scholar 

  120. Dales JP, Garcia S, Carpentier S, Andrac L, et al. Prediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n=905). Br J Cancer 2004;90:1216–1221.

    Article  CAS  PubMed  Google Scholar 

  121. Dales JP, Garcia S, Bonnier P, et al. CD105 expression is a marker of high metastatic risk and poor outcome in breast carcinomas. Correlations between immunohistochemical analysis and long-term follow-up in a series of 929 patients. Am J Clin Pathol 2003;119:374–380.

    Article  PubMed  Google Scholar 

  122. Dales JP, Garcia S, Andrac L, et al. Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: correlation with long-term patient outcome. Int J Oncol 2004;24:1197–204.

    PubMed  Google Scholar 

  123. Yao Y, Kubota T, Takeuchi H, Sato K. Prognostic significance of microvessel density determined by an anti-CD105/endoglin monoclonal antibody in astrocytic tumors: comparison with an anti-CD31 monoclonal antibody. Neuropathology 2005;25:201–206.

    Article  PubMed  Google Scholar 

  124. Saad RS, Liu YL, Nathan G, Celebrezze J, Medich D, Silverman JF. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol 2004;17:197–203.

    Article  CAS  PubMed  Google Scholar 

  125. Adam M, Schmidt D, Wardelmann E, Wernert N, Albers P. Angiogenetic protooncogene ets-1 induced neovascularization is involved in the metastatic process of testicular germ cell tumors. Eur Urol 2003;44:329–336.

    Article  CAS  PubMed  Google Scholar 

  126. Tanaka F, Otake Y, Yanagihara K, et al. Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody. Clin Cancer Res 2001;7: 3410–3415.

    CAS  PubMed  Google Scholar 

  127. Josefsson A, Wikstrom P, Granfors T, et al. Tumor size, vascular density and proliferation as prognostic markers in GS 6 and GS 7 prostate tumors in patients with long follow-up and non-curative treatment. Eur Urol 2005;48:577–583.

    Article  PubMed  Google Scholar 

  128. Yu JX, Zhang XT, Liao YQ, et al. Relationship between expression of CD105 and growth factors in malignant tumors of gastrointestinal tract and its significance. World J Gastroenterol 2003;9:2866–2869.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy

    Ester Fonsatti PhD & Michele Maio MD, PhD

  2. Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, Aviano, Italy

    Michele Maio MD, PhD

Authors
  1. Ester Fonsatti PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michele Maio MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press

About this chapter

Cite this chapter

Fonsatti, E., Maio, M. (2008). Endoglin (CD105): A Strong Candidate for Immunologic Targeting of Tumor Neovasculature in Human Malignancies. In: Transforming Growth Factor-β in Cancer Therapy, Volume I. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-292-2_25

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-292-2_25

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-714-3

  • Online ISBN: 978-1-59745-292-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation