Skip to main content
SpringerLink
Log in

Tumor Blood Vessels as Targets for Cancer Therapy

  • Chapter
  • First Online:
Book cover Cancer Drug Delivery Systems Based on the Tumor Microenvironment

  • 647 Accesses

Abstract

Tumor growth and metastasis are dependent on angiogenesis, which is the formation of new blood vessels. The newly formed blood vessels around the tumor supply oxygen and nutrients to the tumor, supporting its progression. Moreover, these blood vessels also serve as channels through which tumor cells metastasize to distant organs. Tumor blood vessels, and especially the endothelial cells lining tumor blood vessels [tumor endothelial cells (TECs)], are important targets in cancer therapy. Since newly formed tumor blood vessels originate from pre-existing normal vessels, tumor blood vessels and TECs traditionally have been considered the same as normal vasculature. Tumor blood vessels, however, have a distinctively abnormal phenotype, including morphological alterations. Recently, it has been revealed that TECs constitute a heterogeneous population, exhibiting characteristics induced largely by tumor microenvironmental factors. Furthermore, TECs induce cancer progression through metastasis passively but also actively. This chapter will review the mechanisms underlying tumor angiogenesis and discuss the biology of TECs, offering new perspectives on treatment strategies that can target tumor blood vessels from a personalized medicine perspective.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
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

References

  1. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186

    Article  CAS  PubMed  Google Scholar 

  2. Folkman J, Kerbel R (2002) Role of angiogenesis in tumor growth and metastasis. Clinical translation of angiogenesis inhibitors. Semin Oncol 29(6 Suppl 16):15–18

    Article  CAS  PubMed  Google Scholar 

  3. Nielsen M, Thomsen JL, Primdahl S, Dyreborg U, Andersen JA (1987) Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies. Br J Cancer 56(6):814–819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6(4):273–286

    Article  CAS  PubMed  Google Scholar 

  5. Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3(6):401–410

    Article  CAS  PubMed  Google Scholar 

  6. Goh PP, Sze DM, Roufogalis BD (2007) Molecular and cellular regulators of cancer angiogenesis. Curr Cancer Drug Targets 7(8):743–758

    Article  CAS  PubMed  Google Scholar 

  7. Watanabe K, Hasegawa Y, Yamashita H, Shimizu K, Ding Y, Abe M et al (2004) Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis. J Clin Invest 114(7):898–907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Minami T, Yano K, Miura M, Kobayashi M, Suehiro J, Reid PC et al (2009) The down syndrome critical region gene 1 short variant promoters direct vascular bed-specific gene expression during inflammation in mice. J Clin Invest 119(8):2257–2270

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Folkman J (2006) Antiangiogenesis in cancer therapy–endostatin and its mechanisms of action. Exp Cell Res 312(5):594–607

    Article  CAS  PubMed  Google Scholar 

  10. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM et al (2004) Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 22(11):2184–2191

    Article  CAS  PubMed  Google Scholar 

  11. Keedy VL, Sandler AB (2007) Inhibition of angiogenesis in the treatment of non-small cell lung cancer. Cancer Sci 98(12):1825–1830

    Article  CAS  PubMed  Google Scholar 

  12. Kindler HL, Friberg G, Singh DA, Locker G, Nattam S, Kozloff M et al (2005) Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 23(31):8033–8040

    Article  CAS  PubMed  Google Scholar 

  13. Saif MW, Elfiky A, Salem RR (2007) Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 14(6):1860–1869

    Article  PubMed  Google Scholar 

  14. McDonald DM, Choyke PL (2003) Imaging of angiogenesis: from microscope to clinic. Nat Med 9(6):713–725

    Article  CAS  PubMed  Google Scholar 

  15. Hashizume H, Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S et al (2000) Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol 156(4):1363–1380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kalluri R (2003) Basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer 3(6):422–433

    Article  CAS  PubMed  Google Scholar 

  17. Baluk P, Hashizume H, McDonald DM (2005) Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev 15(1):102–111

    Article  CAS  PubMed  Google Scholar 

  18. McDonald DM, Baluk P (2002) Significance of blood vessel leakiness in cancer. Cancer Res 62(18):5381–5385

    CAS  PubMed  Google Scholar 

  19. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307(5706):58–62

    Article  CAS  PubMed  Google Scholar 

  20. Chang YS, di Tomaso E, McDonald DM, Jones R, Jain RK, Munn LL (2000) Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci U S A 97(26):14608–14613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46(12 Pt 1):6387–6392

    CAS  PubMed  Google Scholar 

  22. Fang J, Nakamura H, Maeda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 63(3):136–151

    Article  CAS  PubMed  Google Scholar 

  23. Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F et al (2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15(3):220–231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhang L, Takara K, Yamakawa D, Kidoya H, Takakura N (2015) Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy. Cancer Sci 107(1):36–44

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Ohga N, Ishikawa S, Maishi N, Akiyama K, Hida Y, Kawamoto T et al (2012) Heterogeneity of tumor endothelial cells: comparison between tumor endothelial cells isolated from high- and low-metastatic tumors. Am J Pathol 180(3):1294–1307

    Article  CAS  PubMed  Google Scholar 

  26. Langenkamp E, Molema G (2009) Microvascular endothelial cell heterogeneity: general concepts and pharmacological consequences for anti-angiogenic therapy of cancer. Cell Tissue Res 335(1):205–222

    Article  CAS  PubMed  Google Scholar 

  27. Arap W, Kolonin MG, Trepel M, Lahdenranta J, Cardo-Vila M, Giordano RJ et al (2002) Steps toward mapping the human vasculature by phage display. Nat Med 8(2):121–127

    Article  CAS  PubMed  Google Scholar 

  28. Trepel M, Arap W, Pasqualini R (2002) In vivo phage display and vascular heterogeneity: implications for targeted medicine. Curr Opin Chem Biol 6(3):399–404

    Article  CAS  PubMed  Google Scholar 

  29. St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E et al (2000) Genes expressed in human tumor endothelium. Science 289(5482):1197–1202

    Article  CAS  PubMed  Google Scholar 

  30. Seaman S, Stevens J, Yang MY, Logsdon D, Graff-Cherry C, St Croix B (2007) Genes that distinguish physiological and pathological angiogenesis. Cancer Cell 11(6):539–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Carson-Walter EB, Watkins DN, Nanda A, Vogelstein B, Kinzler KW, St Croix B (2001) Cell surface tumor endothelial markers are conserved in mice and humans. Cancer Res 61(18):6649–6655

    CAS  PubMed  Google Scholar 

  32. Nanda A, St Croix B (2004) Tumor endothelial markers: new targets for cancer therapy. Curr Opin Oncol 16(1):44–49

    Article  CAS  PubMed  Google Scholar 

  33. Hida K, Hida Y, Amin DN, Flint AF, Panigrahy D, Morton CC et al (2004) Tumor-associated endothelial cells with cytogenetic abnormalities. Cancer Res 64(22):8249–8255

    Article  CAS  PubMed  Google Scholar 

  34. Hida K, Klagsbrun M (2005) A new perspective on tumor endothelial cells: unexpected chromosome and centrosome abnormalities. Cancer Res 65(7):2507–2510

    Article  CAS  PubMed  Google Scholar 

  35. Amin DN, Hida K, Bielenberg DR, Klagsbrun M (2006) Tumor endothelial cells express epidermal growth factor receptor (EGFR) but not ErbB3 and are responsive to EGF and to EGFR kinase inhibitors. Cancer Res 66(4):2173–2180

    Article  CAS  PubMed  Google Scholar 

  36. Tsuchiya K, Hida K, Hida Y, Muraki C, Ohga N, Akino T et al (2010) Adrenomedullin antagonist suppresses tumor formation in renal cell carcinoma through inhibitory effects on tumor endothelial cells and endothelial progenitor mobilization. Int J Oncol 36(6):1379–1386

    PubMed  Google Scholar 

  37. Matsuda K, Ohga N, Hida Y, Muraki C, Tsuchiya K, Kurosu T et al (2010) Isolated tumor endothelial cells maintain specific character during long-term culture. Biochem Biophys Res Commun 394(4):947–954

    Article  CAS  PubMed  Google Scholar 

  38. Bussolati B, Deambrosis I, Russo S, Deregibus MC, Camussi G (2003) Altered angiogenesis and survival in human tumor-derived endothelial cells. FASEB J 17(9):1159–1161

    Article  CAS  PubMed  Google Scholar 

  39. Matsuda K, Ohga N, Hida Y, Muraki C, Tsuchiya K, Kurosu T et al (2010) Isolated tumor endothelial cells maintain specific character during long-term culture. Biochem Biophys Res Commun 394:947–954

    Article  CAS  PubMed  Google Scholar 

  40. Bussolati B, Grange C, Bruno S, Buttiglieri S, Deregibus MC, Tei L et al (2006) Neural-cell adhesion molecule (NCAM) expression by immature and tumor-derived endothelial cells favors cell organization into capillary-like structures. Exp Cell Res 312(6):913–924

    Article  CAS  PubMed  Google Scholar 

  41. Fonsato V, Buttiglieri S, Deregibus MC, Puntorieri V, Bussolati B, Camussi G (2006) Expression of Pax2 in human renal tumor-derived endothelial cells sustains apoptosis resistance and angiogenesis. Am J Pathol 168(2):706–713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ohmura-Kakutani H, Akiyama K, Maishi N, Ohga N, Hida Y, Kawamoto T et al (2014) Identification of tumor endothelial cells with high aldehyde dehydrogenase activity and a highly angiogenic phenotype. PLoS One 9(12):e113910

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Hida K, Maishi N, Akiyama K, Ohmura-Kakutani H, Torii C, Ohga N et al (2017) Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance. Cancer Sci 108:2195–2203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Akino T, Hida K, Hida Y, Tsuchiya K, Freedman D, Muraki C et al (2009) Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors. Am J Pathol 175(6):2657–2667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ricci-Vitiani L, Pallini R, Biffoni M, Todaro M, Invernici G, Cenci T et al (2010) Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 468(7325):824–828

    Article  CAS  PubMed  Google Scholar 

  46. Wang R, Chadalavada K, Wilshire J, Kowalik U, Hovinga KE, Geber A et al (2010) Glioblastoma stem-like cells give rise to tumour endothelium. Nature 468(7325):829–833

    Article  CAS  PubMed  Google Scholar 

  47. Xiong YQ, Sun HC, Zhang W, Zhu XD, Zhuang PY, Zhang JB et al (2009) Human hepatocellular carcinoma tumor-derived endothelial cells manifest increased angiogenesis capability and drug resistance compared with normal endothelial cells. Clin Cancer Res 15(15):4838–4846

    Article  CAS  PubMed  Google Scholar 

  48. Akiyama K, Ohga N, Hida Y, Kawamoto T, Sadamoto Y, Ishikawa S et al (2012) Tumor endothelial cells acquire drug resistance by MDR1 up-regulation via VEGF signaling in tumor microenvironment. Am J Pathol 180(3):1283–1293

    Article  CAS  PubMed  Google Scholar 

  49. Mundhekar AN, Bullard DC, Kucik DF (2006) Intracellular heterogeneity in adhesiveness of endothelium affects early steps in leukocyte adhesion. Am J Physiol Cell Physiol 291(1):C130–C137

    Article  CAS  PubMed  Google Scholar 

  50. Molema G (2010) Heterogeneity in endothelial responsiveness to cytokines, molecular causes, and pharmacological consequences. Semin Thromb Hemost 36(3):246–264

    Article  CAS  PubMed  Google Scholar 

  51. Naito H, Kidoya H, Sakimoto S, Wakabayashi T, Takakura N (2011) Identification and characterization of a resident vascular stem/progenitor cell population in preexisting blood vessels. EMBO J 31(4):842–855

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Saubamea B, Cochois-Guegan V, Cisternino S, Scherrmann JM (2012) Heterogeneity in the rat brain vasculature revealed by quantitative confocal analysis of endothelial barrier antigen and P-glycoprotein expression. J Cereb Blood Flow Metab 32(1):81–92

    Article  CAS  PubMed  Google Scholar 

  53. Dudley AC, Khan ZA, Shih SC, Kang SY, Zwaans BM, Bischoff J, Klagsbrun M (2008) Calcification of multipotent prostate tumor endothelium. Cancer cell 14(3):201–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Naito H, Wakabayashi T, Kidoya H, Muramatsu F, Takara K, Eino D, Yamane K, Iba T, Takakura N (2016) Endothelial side population cells contribute to tumor angiogenesis and anti-angiogenic drug resistance. Cancer Res 76(11):3200–3210

    Article  CAS  PubMed  Google Scholar 

  55. Nagy JA, Dvorak HF (2012) Heterogeneity of the tumor vasculature: the need for new tumor blood vessel type-specific targets. Clin Exp Metastasis 29(7):657–662

    Article  CAS  Google Scholar 

  56. Bussolati B, Assenzio B, Deregibus MC, Camussi G (2006) The proangiogenic phenotype of human tumor-derived endothelial cells depends on thrombospondin-1 downregulation via phosphatidylinositol 3-kinase/Akt pathway. J Mol Med (Berl) 84(10):852–863

    Article  CAS  Google Scholar 

  57. Adya R, Tan BK, Punn A, Chen J, Randeva HS (2008) Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis. Cardiovasc Res 78(2):356–365

    Article  CAS  PubMed  Google Scholar 

  58. Duensing S, Munger K (2002) Human papillomaviruses and centrosome duplication errors: modeling the origins of genomic instability. Oncogene 21(40):6241–6248

    Article  CAS  PubMed  Google Scholar 

  59. Hida K, Hida Y, Shindoh M (2008) Understanding tumor endothelial cell abnormalities to develop ideal anti-angiogenic therapies. Cancer Sci 99(3):459–466

    Article  CAS  PubMed  Google Scholar 

  60. Sato Y (2011) Persistent vascular normalization as an alternative goal of anti-angiogenic cancer therapy. Cancer Sci 102(7):1253–1256

    Article  CAS  PubMed  Google Scholar 

  61. Helfrich I, Scheffrahn I, Bartling S, Weis J, von Felbert V, Middleton M et al (2010) Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma. J Exp Med 207(3):491–503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gao D, Nolan D, McDonnell K, Vahdat L, Benezra R, Altorki N et al (2009) Bone marrow-derived endothelial progenitor cells contribute to the angiogenic switch in tumor growth and metastatic progression. Biochim Biophys Acta 1796(1):33–40

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Taylor SM, Nevis KR, Park HL, Rogers GC, Rogers SL, Cook JG et al (2010) Angiogenic factor signaling regulates centrosome duplication in endothelial cells of developing blood vessels. Blood 116(16):3108–3117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kondoh M, Ohga N, Akiyama K, Hida Y, Maishi N, Towfik AM et al (2013) Hypoxia-induced reactive oxygen species cause chromosomal abnormalities in endothelial cells in the tumor microenvironment. PLoS One 8(11):e80349

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Butler JM, Kobayashi H, Rafii S (2010) Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors. Nat Rev Cancer 10(2):138–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Cao Z, Ding BS, Guo P, Lee SB, Butler JM, Casey SC et al (2014) Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance. Cancer Cell 25(3):350–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Cao Z, Scandura JM, Inghirami GG, Shido K, Ding BS, Rafii S (2017) Molecular checkpoint decisions made by subverted vascular niche transform indolent tumor cells into Chemoresistant Cancer stem cells. Cancer Cell 31(1):110–126

    Article  CAS  PubMed  Google Scholar 

  68. Zhu TS, Costello MA, Talsma CE, Flack CG, Crowley JG, Hamm LL et al (2011) Endothelial cells create a stem cell niche in glioblastoma by providing NOTCH ligands that nurture self-renewal of cancer stem-like cells. Cancer Res 71(18):6061–6072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Pedrosa AR, Trindade A, Carvalho C, Graca J, Carvalho S, Peleteiro MC et al (2015) Endothelial Jagged1 promotes solid tumor growth through both pro-angiogenic and angiocrine functions. Oncotarget 6(27):24404–24423

    Article  PubMed  PubMed Central  Google Scholar 

  70. Wieland E, Rodriguez-Vita J, Liebler SS, Mogler C, Moll I, Herberich SE et al (2017) Endothelial Notch1 activity facilitates metastasis. Cancer Cell 31(3):355–367

    Article  CAS  PubMed  Google Scholar 

  71. Maishi N, Ohba Y, Akiyama K, Ohga N, Hamada J, Nagao-Kitamoto H et al (2016) Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan. Sci Rep 6:28039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. van Beijnum JR, Dings RP, van der Linden E, Zwaans BM, Ramaekers FC, Mayo KH et al (2006) Gene expression of tumor angiogenesis dissected: specific targeting of colon cancer angiogenic vasculature. Blood 108(7):2339–2348

    Article  PubMed  CAS  Google Scholar 

  73. Lu C, Bonome T, Li Y, Kamat AA, Han LY, Schmandt R et al (2007) Gene alterations identified by expression profiling in tumor-associated endothelial cells from invasive ovarian carcinoma. Cancer Res 67(4):1757–1768

    Article  CAS  PubMed  Google Scholar 

  74. Buckanovich RJ, Sasaroli D, O’Brien-Jenkins A, Botbyl J, Hammond R, Katsaros D et al (2007) Tumor vascular proteins as biomarkers in ovarian cancer. J Clin Oncol 25(7):852–861

    Article  CAS  PubMed  Google Scholar 

  75. Muraki C, Ohga N, Hida Y, Nishihara H, Kato Y, Tsuchiya K et al (2012) Cyclooxygenase-2 inhibition causes antiangiogenic effects on tumor endothelial and vascular progenitor cells. Int J Cancer 130(1):59–70

    Article  CAS  PubMed  Google Scholar 

  76. Yamamoto K, Ohga N, Hida Y, Maishi N, Kawamoto T, Kitayama K et al (2012) Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells. Br J Cancer 106(6):1214–1223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Maishi N, Ohga N, Hida Y, Akiyama K, Kitayama K, Osawa T et al (2012) CXCR7: a novel tumor endothelial marker in renal cell carcinoma. Pathol Int 62(5):309–317

    Article  CAS  PubMed  Google Scholar 

  78. Osawa T, Ohga N, Akiyama K, Hida Y, Kitayama K, Kawamoto T et al (2013) Lysyl oxidase secreted by tumour endothelial cells promotes angiogenesis and metastasis. Br J Cancer 109(8):2237–2247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Osawa T, Ohga N, Hida Y, Kitayama K, Akiyama K, Onodera Y et al (2012) Prostacyclin receptor in tumor endothelial cells promotes angiogenesis in an autocrine manner. Cancer Sci 103(6):1038–1044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Alam MT, Nagao-Kitamoto H, Ohga N, Akiyama K, Maishi N, Kawamoto T et al (2014) Suprabasin as a novel tumor endothelial cell marker. Cancer Sci 105(12):1533–1540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Otsubo T, Hida Y, Ohga N, Sato H, Kai T, Matsuki Y et al (2014) Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells. Cancer Sci 105(5):560–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhuang X, Herbert JM, Lodhia P, Bradford J, Turner AM, Newby PM et al (2015) Identification of novel vascular targets in lung cancer. Br J Cancer 112(3):485–494

    Article  CAS  PubMed  Google Scholar 

  83. Pasqualini R, Koivunen E, Kain R, Lahdenranta J, Sakamoto M, Stryhn A et al (2000) Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res 60(3):722–727

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Pastorino F, Brignole C, Marimpietri D, Cilli M, Gambini C, Ribatti D et al (2003) Vascular damage and anti-angiogenic effects of tumor vessel-targeted liposomal chemotherapy. Cancer Res 63(21):7400–7409

    CAS  PubMed  Google Scholar 

  85. Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279(5349):377–380

    Article  CAS  PubMed  Google Scholar 

  86. Kogure K, Akita H, Yamada Y, Harashima H (2008) Multifunctional envelope-type nano device (MEND) as a non-viral gene delivery system. Adv Drug Deliv Rev 60(4–5):559–571

    Article  CAS  PubMed  Google Scholar 

  87. Hatakeyama H, Akita H, Harashima H (2011) A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma. Adv Drug Deliv Rev 63(3):152–160

    Article  CAS  PubMed  Google Scholar 

  88. Sato Y, Hatakeyama H, Sakurai Y, Hyodo M, Akita H, Harashima H (2012) A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and gene silencing activity in vitro and in vivo. J Control Release 163(3):267–276

    Article  CAS  PubMed  Google Scholar 

  89. Sakurai Y, Hatakeyama H, Sato Y, Hyodo M, Akita H, Ohga N et al (2014) RNAi-mediated gene knockdown and anti-angiogenic therapy of RCCs using a cyclic RGD-modified liposomal-siRNA system. J Control Release 173:110–118

    Article  CAS  PubMed  Google Scholar 

  90. Whitehead KA, Langer R, Anderson DG (2009) Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8(2):129–138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank Editors from Enago, for editing a draft of this manuscript.

We also thank members of the Department of Vascular Biology, Institute for Genetic Medicine, Hokkaido University.

Conflict of Interest

None declared.

Author information

Authors and Affiliations

  1. Vascular Biology and Molecular Pathology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan

    Kyoko Hida & Nako Maishi

  2. Department of Cardiovascular and Thoracic Surgery, Faculty of Medicine, Hokkaido University, Sapporo, Japan

    Yasuhiro Hida

Authors
  1. Kyoko Hida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nako Maishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasuhiro Hida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyoko Hida .

Editor information

Editors and Affiliations

  1. Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan

    Yasuhiro Matsumura

  2. Moores UCSD Cancer Center and Department of Pathology, University of California San Diego, La Jolla, CA, USA

    David Tarin

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Japan KK, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hida, K., Maishi, N., Hida, Y. (2019). Tumor Blood Vessels as Targets for Cancer Therapy. In: Matsumura, Y., Tarin, D. (eds) Cancer Drug Delivery Systems Based on the Tumor Microenvironment. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56880-3_3

Download citation

Publish with us

Policies and ethics

Search

Navigation