Skip to main content
SpringerLink
Log in

Endothelial Cells and Cancer

  • Chapter
The Vascular Endothelium II

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 176/II))

Abstract

Endothelial cells play a key role in the development and function of blood and lymph vessels. Excessive proliferation and transformation of endothelial cells lead to pathological angiogenesis/lymphangiogenesis or vascular malfunctions which are hallmarks of malignant disorders. There is emerging evidence that circulating endothelial progenitor cells (EPCs) also contribute significantly to these processes. Major progress has been achieved over the past few years in the identification of key molecules involved, and in targeting tumour angiogenesis for human therapy. Current research efforts are concentrated on deciphering the origin and functional properties of endotheliumin various tumours, as well as endothelial neoplasms themselves. The aim of these studies is to investigate the molecular mechanisms regulating mobilisation of EPCs from bone marrow, and their homing and differentiation into mature endotheliumin situ at sites of neovascularisation, as well as the role of viral oncogenes in regulating the plasticity and extending the life span of endothelial cells. Integrated understanding of the mechanisms regulating the properties and function of endothelial cells during tumourigenesis is resulting in the development of a number of exciting and bold approaches for the treatment of cancer.

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 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
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

  • Achen MG, Jeltsch M, Kukk E, Makinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA (1998) Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci U S A 95:548–553

    Article  PubMed  CAS  Google Scholar 

  • Aird WC, Edelberg JM, Weiler-Guettler H, Simmons WW, Smith TW, Rosenberg RD (1997) Vascular bed-specific expression of an endothelial cell gene is programmed by the tissue microenvironment. J Cell Biol 138:1117–1124

    Article  PubMed  CAS  Google Scholar 

  • Albini A, Benelli R, Presta M, Rusnati M, Ziche M, Rubartelli A, Paglialunga G, Bussolino F, Noonan D (1996a) HIV-tat protein is a heparin-binding angiogenic growth factor. Oncogene 12:289–297

    PubMed  CAS  Google Scholar 

  • Alitalo K, Carmeliet P (2002) Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell 1:219–227

    Article  PubMed  CAS  Google Scholar 

  • Alitalo K, Tammela T, Petrova TV (2005) Lymphangiogenesis in development and human disease. Nature 438:946–953

    Article  PubMed  CAS  Google Scholar 

  • Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279:377–380

    Article  PubMed  CAS  Google Scholar 

  • Asahara T, Isner JM (2002) Endothelial progenitor cells for vascular regeneration. J Hematother Stem Cell Res 11:171–178

    Article  PubMed  Google Scholar 

  • Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964–3972

    Article  PubMed  CAS  Google Scholar 

  • Asahara T, Kalka C, Isner JM (2000) Stem cell therapy and gene transfer for regeneration. Gene Ther 7:451–457

    Article  PubMed  CAS  Google Scholar 

  • Bagley RG, Walter-Yohrling J, Cao X, Weber W, Simons B, Cook BP, Chartrand SD, Wang C, Madden SL, Teicher BA (2003) Endothelial precursor cells as a model of tumor endothelium: characterization and comparison with mature endothelial cells. Cancer Res 63:5866–5873

    PubMed  CAS  Google Scholar 

  • Bais C, Van Geelen A, Flores P, Mutlu A, Chiozzini C, Dias S, Silverstein RL, Rafii S, Mesri EA (2003) Kaposi’s sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/KDR. Cancer Cell 3:131–143

    Article  PubMed  CAS  Google Scholar 

  • Beasley NJ, Prevo R, Banerji S, Leek RD, Moore J, van T P, Cox G, Harris AL, Jackson DG (2002) Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res 62:1315–1320

    PubMed  CAS  Google Scholar 

  • Bell CD (2003) Endothelial cell tumors. Microsc Res Tech 60:165–170

    Article  PubMed  Google Scholar 

  • Bertolini F, Paul S, Mancuso P, Monestiroli S, Gobbi A, Shaked Y, Kerbel RS (2003) Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res 63: 4342–4346

    PubMed  CAS  Google Scholar 

  • Bielenberg DR, Bucana CD, Sanchez R, Mulliken JB, Folkman J, Fidler IJ (1999) Progressive growth of infantile cutaneous hemangiomas is directly correlated with hyperplasia and angiogenesis of adjacent epidermis and inversely correlated with expression of the endogenous angiogenesis inhibitor, IFN-beta. Int J Oncol 14:401–408

    PubMed  CAS  Google Scholar 

  • Boshoff C, Weiss R (2002) AIDS-related malignancies. Nat Rev Cancer 2:373–382

    Article  PubMed  CAS  Google Scholar 

  • Boshoff C, Schulz TF, Kennedy MM, Graham AK, Fisher C, Thomas A, McGee JO, Weiss RA, O’Leary JJ (1995) Kaposi’s sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med 1:1274–1278

    Article  PubMed  CAS  Google Scholar 

  • Boshoff C, Endo Y, Collins PD, Takeuchi Y, Reeves JD, Schweickart VL, Siani MA, Sasaki T, Williams TJ, Gray PW, Moore PS, Chang Y, Weiss RA (1997) Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines. Science 278:290–294

    Article  PubMed  CAS  Google Scholar 

  • Brown LF, Dezube BJ, Tognazzi K, Dvorak HF, Yancopoulos GD (2000) Expression of Tie1, Tie2, and angiopoietins 1, 2, and 4 in Kaposi’s sarcoma and cutaneous angiosarcoma. Am J Pathol 156:2179–2183

    PubMed  CAS  Google Scholar 

  • Brugarolas J, Kaelin WG Jr (2004) Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma syndromes. Cancer Cell 6:7–10

    Article  PubMed  CAS  Google Scholar 

  • Capillo M, Mancuso P, Gobbi A, Monestiroli S, Pruneri G, Dell’Agnola C, Martinelli G, Shultz L, Bertolini F (2003) Continuous infusion of endostatin inhibits differentiation, mobilization, and clonogenic potential of endothelial cell progenitors. Clin Cancer Res 9:377–382

    PubMed  CAS  Google Scholar 

  • Carmeliet P (2000) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6:389–395

    Article  PubMed  CAS  Google Scholar 

  • Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9:653–660

    Article  PubMed  CAS  Google Scholar 

  • Carmeliet P, Collen D (1999) Role of vascular endothelial growth factor and vascular endothelial growth factor receptors in vascular development. Curr Top Microbiol Immunol 237:133–158

    PubMed  CAS  Google Scholar 

  • Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257

    Article  PubMed  CAS  Google Scholar 

  • Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435–439

    Article  PubMed  CAS  Google Scholar 

  • Carson-Walter EB, Watkins DN, Nanda A, Vogelstein B, Kinzler KW, St CB (2001) Cell surface tumor endothelial markers are conserved in mice and humans. Cancer Res 61:6649–6655

    PubMed  CAS  Google Scholar 

  • Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266:1865–1869

    Article  PubMed  CAS  Google Scholar 

  • Chang Y, Moore PS, Talbot SJ, Boshoff CH, Zarkowska T, Godden K, Paterson H, Weiss RA, Mittnacht S (1996b) Cyclin encoded by KS herpesvirus. Nature 382:410

    Article  PubMed  CAS  Google Scholar 

  • Chi JT, Chang HY, Haraldsen G, Jahnsen FL, Troyanskaya OG, Chang DS, Wang Z, Rockson SG, van de R M, Botstein D, Brown PO (2003) Endothelial cell diversity revealed by global expression profiling. Proc Natl Acad Sci U S A 100:10623–10628

    Article  PubMed  CAS  Google Scholar 

  • Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, Delfino JJ, Siegel NR, Leimgruber RM, Feder J (1989a) Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest 84:1470–1478

    PubMed  CAS  Google Scholar 

  • Connolly DT, Olander JV, Heuvelman D, Nelson R, Monsell R, Siegel N, Haymore BL, Leimgruber R, Feder J (1989b) Human vascular permeability factor. Isolation from U937 cells. J Biol Chem 264:20017–20024

    PubMed  CAS  Google Scholar 

  • Coultas L, Chawengsaksophak K, Rossant J (2005) Endothelial cells and VEGF in vascular development. Nature 438:937–945

    Article  PubMed  CAS  Google Scholar 

  • Dadras SS, Paul T, Bertoncini J, Brown LF, Muzikansky A, Jackson DG, Ellwanger U, Garbe C, Mihm MC, Detmar M (2003) Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival. Am J Pathol 162:1951–1960

    PubMed  Google Scholar 

  • Dadras SS, North PE, Bertoncini J, Mihm MC, Detmar M (2004) Infantile hemangiomas are arrested in an early developmental vascular differentiation state. Mod Pathol 17: 1068–1079

    Article  PubMed  Google Scholar 

  • De Palma M, Venneri MA, Roca C, Naldini L (2003) Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nat Med 9:789–795

    Article  PubMed  CAS  Google Scholar 

  • Dong J, Grunstein J, Tejada M, Peale F, Frantz G, Liang WC, Bai W, Yu L, Kowalski J, Liang X, Fuh G, Gerber HP, Ferrara N (2004) VEGF-null cells require PDGFR alpha signaling-mediated stromal fibroblast recruitment for tumorigenesis. EMBO J 23:2800–2810

    Article  PubMed  CAS  Google Scholar 

  • Eliceiri BP, Cheresh DA (1999) The role of alphav integrins during angiogenesis: insights into potential mechanisms of action and clinical development. J Clin Invest 103:1227–1230

    PubMed  CAS  Google Scholar 

  • Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581–611

    Article  PubMed  CAS  Google Scholar 

  • Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438:967–974

    Article  PubMed  CAS  Google Scholar 

  • Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MW (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439–442

    Article  PubMed  CAS  Google Scholar 

  • Flore O, Rafii S, Ely S, O’Leary JJ, Hyjek EM, Cesarman E (1998) Transformation of primary human endothelial cells by Kaposi’s sarcoma-associated herpesvirus. Nature 394: 588–592

    Article  PubMed  CAS  Google Scholar 

  • Fong GH, Zhang L, Bryce DM, Peng J (1999) Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice. Development 126:3015–3025

    PubMed  CAS  Google Scholar 

  • Fox SB, Harris AL (2004) Histological quantitation of tumour angiogenesis. APMIS 112: 413–430

    Article  PubMed  Google Scholar 

  • Gerber HP, Hillan KJ, Ryan AM, Kowalski J, Keller GA, Rangell L, Wright BD, Radtke F, Aguet M, Ferrara N (1999) VEGF is required for growth and survival in neonatal mice. Development 126:1149–1159

    PubMed  CAS  Google Scholar 

  • Gerber HP, Malik AK, Solar GP, Sherman D, Liang XH, Meng G, Hong K, Marsters JC, Ferrara N (2002) VEGF regulates haematopoietic stemcell survival by an internal autocrine loop mechanism. Nature 417:954–958

    Article  PubMed  CAS  Google Scholar 

  • Harris AL (2002) Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer 2:38–47

    Article  PubMed  CAS  Google Scholar 

  • Hattori K, Dias S, Heissig B, Hackett NR, Lyden D, Tateno M, Hicklin DJ, Zhu Z, Witte L, Crystal RG, Moore MA, Rafii S (2001) Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 193:1005–1014

    Article  PubMed  CAS  Google Scholar 

  • Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B, Hicklin DJ, Zhu Z, Bohlen P, Witte L, Hendrikx J, Hackett NR, Crystal RG, Moore MA, Werb Z, Lyden D, Rafii S (2002) Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 8:841–849

    PubMed  CAS  Google Scholar 

  • He Y, Kozaki K, Karpanen T, Koshikawa K, Yla-Herttuala S, Takahashi T, Alitalo K (2002) Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. J Natl Cancer Inst 94:819–825

    PubMed  CAS  Google Scholar 

  • Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S (2003) Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 102:1340–1346

    Article  PubMed  CAS  Google Scholar 

  • Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109:625–637

    Article  PubMed  CAS  Google Scholar 

  • Hirakawa S, Kodama S, Kunstfeld R, Kajiya K, Brown LF, Detmar M (2005) VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J Exp Med 201:1089–1099

    Article  PubMed  CAS  Google Scholar 

  • Hong YK, Foreman K, Shin JW, Hirakawa S, Curry CL, Sage DR, Libermann T, Dezube BJ, Fingeroth JD, Detmar M (2004) Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus. Nat Genet 36:683–685

    Article  PubMed  CAS  Google Scholar 

  • Huang HY, Ho CC, Huang PH, Hsu SM (2001) Co-expression of VEGF-C and its receptors, VEGFR-2 and VEGFR-3, in endothelial cells of lymphangioma. Implication in autocrine or paracrine regulation of lymphangioma. Lab Invest 81:1729–1734

    PubMed  CAS  Google Scholar 

  • Huang X, Molema G, King S, Watkins L, Edgington TS, Thorpe PE (1997) Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature. Science 275:547–550

    Article  PubMed  CAS  Google Scholar 

  • Iwami Y, Masuda H, Asahara T (2004) Endothelial progenitor cells: past, state of the art, and future. J Cell Mol Med 8:488–497

    PubMed  Google Scholar 

  • Jain RK, Koenig GC, Dellian M, Fukumura D, Munn LL, Melder RJ (1996) Leukocyte-endothelial adhesion and angiogenesis in tumors. Cancer Metastasis Rev 15:195–204

    Article  PubMed  CAS  Google Scholar 

  • Jain RK, Safabakhsh N, Sckell A, Chen Y, Jiang P, Benjamin L, Yuan F, Keshet E (1998) Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: role of vascular endothelial growth factor. Proc Natl Acad Sci U S A 95:10820–10825

    Article  PubMed  CAS  Google Scholar 

  • Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K (1996) A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 15:1751

    PubMed  CAS  Google Scholar 

  • Kaipainen A, Korhonen J, Mustonen T, van Hinsbergh VW, Fang GH, Dumont D, Breitman M, Alitalo K (1995) Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci U S A 92:3566–3570

    Article  PubMed  CAS  Google Scholar 

  • Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827

    Article  PubMed  CAS  Google Scholar 

  • Karpanen T, Egeblad M, Karkkainen MJ, Kubo H, Yla-Herttuala S, Jaattela M, Alitalo K (2001) Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res 61:1786–1790

    PubMed  CAS  Google Scholar 

  • Kerbel RS, Klement G, Pritchard KI, Kamen B (2002) Continuous low-dose anti-angiogenic/metronomic chemotherapy: from the research laboratory into the oncology clinic. Ann Oncol 13:12–15

    Article  PubMed  CAS  Google Scholar 

  • Kerjaschki D, Huttary N, Raab I, Regele H, Bojarski-Nagy K, Bartel G, Krober SM, Greinix H, Rosenmaier A, Karlhofer F, Wick N, Mazal PR (2006) Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants. Nat Med 12:230–234

    Article  PubMed  CAS  Google Scholar 

  • Kim KJ, Li B, Winer J, Armanini M, Gillett N, Philips HS, Ferrara N (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841–844

    Article  PubMed  CAS  Google Scholar 

  • Koch AE, Halloran MM, Haskell CJ, Shah MR, Polverini PJ (1995) Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature 376:517–519

    Article  PubMed  CAS  Google Scholar 

  • Lal A, Peters H, St CB, Haroon ZA, Dewhirst MW, Strausberg RL, Kaanders JH, van der Kogel AJ, Riggins GJ (2001) Transcriptional response to hypoxia in human tumors. J Natl Cancer Inst 93:1337–1343

    Article  PubMed  CAS  Google Scholar 

  • Lawson ND, Scheer N, Pham VN, Kim CH, Chitnis AB, Campos-Ortega JA, Weinstein BM (2001) Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development 128:3675–3683

    PubMed  CAS  Google Scholar 

  • LeCouter J, Lin R, Ferrara N (2002) Endocrine gland-derived VEGF and the emerging hypothesis of organ-specific regulation of angiogenesis. Nat Med 8:913–917

    Article  PubMed  CAS  Google Scholar 

  • Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309

    Article  PubMed  CAS  Google Scholar 

  • Lindahl P, Johansson BR, Leveen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277:242–245

    Article  PubMed  CAS  Google Scholar 

  • Luttun A, Carmeliet P (2003) De novo vasculogenesis in the heart. Cardiovasc Res 58:378–389

    Article  PubMed  CAS  Google Scholar 

  • Luttun A, Tjwa M, Carmeliet P (2002) Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic targets for angiogenic disorders. Ann N Y Acad Sci 979:80–93

    Article  PubMed  CAS  Google Scholar 

  • Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O’Reilly R, Bader BL, Hynes RO, Zhuang Y, Manova K, Benezra R (1999) Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 401:670–677

    Article  PubMed  CAS  Google Scholar 

  • Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L, Wu Y, Hicklin D, Zhu Z, Hackett NR, Crystal RG, Moore MA, Hajjar KA, Manova K, Benezra R, Rafii S (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7:1194–1201

    Article  PubMed  CAS  Google Scholar 

  • Makinen T, Veikkola T, Mustjoki S, Karpanen T, Catimel B, Nice EC, Wise L, Mercer A, Kowalski H, Kerjaschki D, Stacker SA, Achen MG, Alitalo K (2001) Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J 20:4762–4773

    Article  PubMed  CAS  Google Scholar 

  • Mandriota SJ, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, Banerji S, Huarte J, Montesano R, Jackson DG, Orci L, Alitalo K, Christofori G, Pepper MS (2001) Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J 20:672–682

    Article  PubMed  CAS  Google Scholar 

  • Maula SM, Luukkaa M, Grenman R, Jackson D, Jalkanen S, Ristamaki R (2003) Intratumoral lymphatics are essential for the metastatic spread and prognosis in squamous cell carcinomas of the head and neck region. Cancer Res 63:1920–1926

    PubMed  CAS  Google Scholar 

  • Oliner J, Min H, Leal J, Yu D, Rao S, You E, Tang X, Kim H, Meyer S, Han SJ, Hawkins N, Rosenfeld R, Davy E, Graham K, Jacobsen F, Stevenson S, Ho J, Chen Q, Hartmann T, Michaels M, Kelley M, Li L, Sitney K, Martin F, Sun JR, Zhang N, Lu J, Estrada J, Kumar R, Coxon A, Kaufman S, Pretorius J, Scully S, Cattley R, Payton M, Coats S, Nguyen L, Desilva B, Ndifor A, Hayward I, Radinsky R, Boone T, Kendall R (2004) Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2. Cancer Cell 6:507–516

    Article  PubMed  CAS  Google Scholar 

  • Oliver G (2004) Lymphatic vasculature development. Nat Rev Immunol 4:35–45

    Article  PubMed  CAS  Google Scholar 

  • Padera TP, Kadambi A, di T E, Carreira CM, Brown EB, Boucher Y, Choi NC, Mathisen D, Wain J, Mark EJ, Munn LL, Jain RK (2002) Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 296:1883–1886

    Article  PubMed  CAS  Google Scholar 

  • Patan S, Munn LL, Jain RK (1996) Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis. Microvasc Res 51:260–272

    Article  PubMed  CAS  Google Scholar 

  • Peters BA, Diaz LA, Polyak K, Meszler L, Romans K, Guinan EC, Antin JH, Myerson D, Hamilton SR, Vogelstein B, Kinzler KW, Lengauer C (2005) Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med 11:261–262

    Article  PubMed  CAS  Google Scholar 

  • Pyakurel P, Pak F, Mwakigonja AR, Kaaya E, Heiden T, Biberfeld P (2006) Recruitment of Kaposi’s sarcoma spindle cells during tumour development. Int J Cancer (in press)

    Google Scholar 

  • Radkov SA, Kellam P, Boshoff C (2000) The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene Hras transforms primary rat cells. Nat Med 6:1121–1127

    Article  PubMed  CAS  Google Scholar 

  • Rafii S (2000) Circulating endothelial precursors: mystery, reality, and promise. J Clin Invest 105:17–19

    Article  PubMed  CAS  Google Scholar 

  • Rafii S, Lyden D, Benezra R, Hattori K, Heissig B (2002) Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nat Rev Cancer 2:826–835

    Article  PubMed  CAS  Google Scholar 

  • Rak J, Filmus J, Finkenzeller G, Grugel S, Marme D, Kerbel RS (1995) Oncogenes as inducers of tumor angiogenesis. Cancer Metastasis Rev 14:263–277

    Article  PubMed  CAS  Google Scholar 

  • Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674

    Article  PubMed  CAS  Google Scholar 

  • Risau W (1998) Development and differentiation of endothelium. Kidney Int Suppl 67:S3–S6

    Article  PubMed  CAS  Google Scholar 

  • Ritter MR, Dorrell MI, Edmonds J, Friedlander SF, Friedlander M (2002) Insulin-like growth factor 2 and potential regulators of hemangioma growth and involution identified by large-scale expression analysis. Proc Natl Acad Sci U S A 99:7455–7460

    Article  PubMed  CAS  Google Scholar 

  • Ruzinova MB, Schoer RA, Gerald W, Egan JE, Pandolfi PP, Rafii S, Manova K, Mittal V, Benezra R (2003) Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. Cancer Cell 4:277–289

    Article  PubMed  CAS  Google Scholar 

  • Sabin FR (1909) On the origin of the lymphatic system from the veins, and the development of the lymph hearts and thoracic duct in the pig. Am J Anat 1:367–389

    Article  Google Scholar 

  • Safran M, Kaelin WG Jr (2003) HIF hydroxylation and the mammalian oxygen-sensing pathway. J Clin Invest 111:779–783

    Article  PubMed  CAS  Google Scholar 

  • Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U, Dimmeler S, Zeiher AM (2005) Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 111:2981–2987

    Article  PubMed  Google Scholar 

  • Seizinger BR, Rouleau GA, Ozelius LJ, Lane AH, Farmer GE, Lamiell JM, Haines J, Yuen JW, Collins D, Majoor-Krakauer D (1988) Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature 332:268–269

    Article  PubMed  CAS  Google Scholar 

  • Senger DR, Perruzzi CA, Feder J, Dvorak HF (1986) Ahighly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res 46:5629–5632

    PubMed  CAS  Google Scholar 

  • Shaked Y, Bocci G, Munoz R, Man S, Ebos JM, Hicklin DJ, Bertolini F, D’Amato R, Kerbel RS (2005) Cellular and molecular surrogate markers to monitor targeted and non-targeted antiangiogenic drug activity and determine optimal biologic dose. Curr Cancer Drug Targets 5:551–559

    Article  PubMed  CAS  Google Scholar 

  • Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376:62–66

    Article  PubMed  CAS  Google Scholar 

  • Shalaby F, Ho J, Stanford WL, Fischer KD, Schuh AC, Schwartz L, Bernstein A, Rossant J (1997) A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 89:981–990

    Article  PubMed  CAS  Google Scholar 

  • Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K, Detmar M (2001) Induction of tumor lymphangiogenesis by VEGF-Cpromotes breast cancer metastasis. Nat Med 7:192–198

    Article  PubMed  CAS  Google Scholar 

  • Spring H, Schuler T, Arnold B, Hammerling GJ, Ganss R (2005) Chemokines direct endothelial progenitors into tumor neovessels. Proc Natl Acad Sci U S A 102:18111–18116

    Article  PubMed  CAS  Google Scholar 

  • St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW (2000) Genes expressed in human tumor endothelium. Science 289:1197–1202

    Article  PubMed  CAS  Google Scholar 

  • Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R, Jackson DG, Nishikawa S, Kubo H, Achen MG (2001) VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med 7:186–191

    Article  PubMed  CAS  Google Scholar 

  • Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T (1999) Ischemia-and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5:434–438

    Article  PubMed  CAS  Google Scholar 

  • Tamaki T, Akatsuka A, Ando K, Nakamura Y, Matsuzawa H, Hotta T, Roy RR, Edgerton VR (2002) Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. J Cell Biol 157:571–577

    Article  PubMed  CAS  Google Scholar 

  • Vikkula M, Boon LM, Mulliken JB, Olsen BR (1998) Molecular basis of vascular anomalies. Trends Cardiovasc Med 8:281–292

    Article  PubMed  CAS  Google Scholar 

  • Wang HW, Trotter MW, Lagos D, Bourboulia D, Henderson S, Makinen T, Elliman S, Flanagan AM, Alitalo K, Boshoff C (2004) Kaposi sarcoma herpesvirus-induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma. Nat Genet 36:687–693

    Article  PubMed  CAS  Google Scholar 

  • Wigle JT, Harvey N, Detmar M, Lagutina I, Grosveld G, Gunn MD, Jackson DG, Oliver G (2002) An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J 21:1505–1513

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi J, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S, Bosch-Marce M, Masuda H, Losordo DW, Isner JM, Asahara T (2003) Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 107:1322–1328

    Article  PubMed  CAS  Google Scholar 

  • Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J (2000) Vascular-specific growth factors and blood vessel formation. Nature 407:242–248

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Wang JF, Chandran B, Persaud K, Pytowski B, Fingeroth J, Groopman JE (2005) Kaposi’s sarcoma-associated herpesvirus activation of vascular endothelial growth factor receptor 3 alters endothelial function and enhances infection. J Biol Chem 280: 26216–26224

    Article  PubMed  CAS  Google Scholar 

  • Zhong TP, Childs S, Leu JP, Fishman MC (2001) Gridlock signalling pathway fashions the first embryonic artery. Nature 414:216–220

    Article  PubMed  CAS  Google Scholar 

  • Zietz C, Rossle M, Haas C, Sendelhofert A, Hirschmann A, Sturzl M, Lohrs U (1998) MDM-2 oncoprotein overexpression, p53 gene mutation, and VEGF up-regulation in angiosarcomas. Am J Pathol 153:1425–1433

    PubMed  CAS  Google Scholar 

  • Zlotnik A (2004) Chemokines in neoplastic progression. Semin Cancer Biol 14:181–185

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CR U.K. Viral Oncology Group, Wolfson Institute for Biomedical Research, UCL, London, WC1E 6BT, UK

    L. Nikitenko & C. Boshoff

Authors
  1. L. Nikitenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Boshoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT, UK

    Salvador Moncada FRCP FRS  & Annie Higgs  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Nikitenko, L., Boshoff, C. (2006). Endothelial Cells and Cancer. In: Moncada, S., Higgs, A. (eds) The Vascular Endothelium II. Handbook of Experimental Pharmacology, vol 176/II. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-36028-X_10

Download citation

Publish with us

Policies and ethics

Search

Navigation