EMAN RESEARCH PUBLISHING | <p>Angiogenic Switches Play a Critical Progression in Cancer</p>
Angiogenesis biology and therapeutics
REVIEWS   (Open Access)

Angiogenic Switches Play a Critical Progression in Cancer

Nozlena A Samad a*, Ahmad Bustamam Abdul b, Rasedee Abdullah b, Heshu Rahman b,d,e KZ Khor a, Max Stanley Chartrand  c

+ Author Affiliations

Journal of Angiotherapy 2(1) 048-055 https://doi.org/10.25163/angiotherapy.11000125480618

Submitted: 04 April 2018  Revised: 04 May 2018  Published: 08 June 2018 


Tumor angiogenesis has become an important research area over the last decade for its crucial role as an essential component of the growth and spread of cancer. A large amount of literature has shown the link between tumor angiogenesis, metastasis, and overall survival of patients. Not all tumors are angiogenesis-derived and the angiogenesis switch is a sign of the ability of tumor and inflammatory cells to produce angiogenesis factors in tumor microenvironment. The condition of genetic stability of endothelial cells plays an important role in this phenomenon as it makes it less likely to build up resistance towards agents aimed at tumor vasculature. Also, the fact that only 0.05% of the adult human body undergoes angiogenesis, the potential side effects of anti-angiogenesis treatment is kept at a minimum. The study, hence, focuses on the role of angiogenesis in tumor development and operating this very particular switch in controlling tumor.    

Keywords: Angiogenesis; Metastasis; Tumors


Ahmad S, Cudmore MJ, Wang K, Hewett P, Potluri R, Fujisawa T, et al. (2010). Angiopoietin-1 induces migration of monocytes in a tie-2 and integrin-independent manner. Hypertension, 56(3), 477–83.
Alexandrakis MG, Passam FH, Dambaki C, Pappa CA, Stathopoulos EN. (2004). The relation between bone marrow angiogenesis and the proliferation index Ki-67 in multiple myeloma. J ClinPathol. 2004 Aug;57(8):856–60.
PMid:15280408 PMCid:PMC1770397
Baron-Menguy C, Bocquet A, Guihot A-L, Chappard D, Amiot M-J, Andriantsitohaina R, et al. (2007). Effects of red wine polyphenols on postischemic neovascularization model in rats: low doses are proangiogenic, high doses antiangiogenic. FASEB J., (13), 3511–21.
Böhm F, Speicher T, Hellerbrand C, Dickson C, Partanen JM, Ornitz DM, et al. (2010). FGF receptors 1 and 2 control chemically induced injury and compound detoxification in regenerating livers of mice. Gastroenterology, 139(4), 1385–96.
PMid:20603121 PMCid:PMC2949525
Brindle NPJ, Saharinen P, Alitalo K. (2006). Signaling and functions of angiopoietin-1 in vascular protection. Circ Res., 98(8), 1014–23.
PMid:16645151 PMCid:PMC2270395
Burri PH, Hlushchuk R, Djonov V. (2004). Intussusceptive angiogenesis: its emergence, its characteristics, and its significance. DevDyn, 231(3), 474–88.
Cai J, Han S, Qing R, Liao D, Law B, Boulton ME. (2011). In pursuit of new anti-angiogenic therapies for cancer treatment. Front Biosci. 16, 803–14.
Chang SC, Ding JL. (2014). Ubiquitination by SAG regulates macrophage survival/death and immune response during infection. Cell Death Differ. Macmillan Publishers Limited.
Daly ME. (2003). Hemostatic Regulators of Tumor Angiogenesis: A Source of Antiangiogenic Agents for Cancer Treatment? Cancer Spectrum Knowl Environ., 95(22), 1660–73.
Duarte A, Hirashima M, Benedito R, Trindade A, Diniz P, Bekman E, et al. (2004). Dosagesensitive requirement for mouse Dll4 in artery development. Genes Dev., 18(20), 2474–8.
PMid:15466159 PMCid:PMC529534
Dudley AC. (2012). Tumor endothelial cells. Cold Spring HarbPerspect Med., 2(3).
PMid:22393533 PMCid:PMC3282494
Duignan IJ, Corcoran E, Pennello A, Plym MJ, Amatulli M, Claros N, et al. (2011). Pleiotropic Stromal Effects of Vascular Endothelial Growth Factor Receptor 2 Antibody Therapy in Renal Cell Carcinoma Models. Neoplasia, 13(1), 49–59.
PMid:21245940 PMCid:PMC3022428
Fan F, Schimming A, Jaeger D, Podar K. (2012). Targeting the tumor microenvironment: focus on angiogenesis. J Oncol., 281261.
PMid:21876693 PMCid:PMC3163131
Folkman J. (2002). Role of angiogenesis in tumor growth and metastasis. SeminOncol., 29(6), 15–8.
Gaulin J, Kotb R, Turcotte E, Berard G, Sawan B, Schmutz G, et al. (2009). Efficacy of thirdline therapy using bevacizumab in a patient with metastatic colorectal cancer. CurrOncol., 16(5), 84–6.
PMid:19862366 PMCid:PMC2768516
Ghosh G, Subramanian I V, Adhikari N, Zhang X, Joshi HP, Basi D, et al. (2010). Hypoxiainduced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis. J Clin Invest., 120(11), 4141–54.
PMid:20972335 PMCid:PMC2964978
Gillies RJ, Gatenby RA. (2007). Hypoxia and adaptive landscapes in the evolution of carcinogenesis. Cancer Metastasis Rev., 26(2), 311–7.
Giuliani N, Storti P, Bolzoni M, Palma BD, Bonomini S. (2011). Angiogenesis and multiple myeloma. Cancer Microenviron., 4(3), 325–37.
PMid:21735169 PMCid:PMC3234322
Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, et al. (2011). Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev., 91(3), 1071–121.
PMid:21742796 PMCid:PMC3258432
Green CE, Liu T, Montel V, Hsiao G, Lester RD, Subramaniam S, et al. (2009). Chemoattractantsignaling between tumor cells and macrophages regulates cancer cell migration, metastasis and neovascularization. PLoS One, 4(8), e6713.
PMid:19696929 PMCid:PMC2725301
Griffioen AW, Molema G. (2000). Angiogenesis: Potentials for Pharmacologic Intervention in the Treatment of Cancer, Cardiovascular Diseases, and Chronic Inflammation. Pharmacol Rev., 52(2), 237–68.
Gupta SC, Kim JH, Prasad S, Aggarwal BB. (2010). Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev, 29(3), 405–34.
PMid:20737283 PMCid:PMC2996866
Gutiérrez J, Brandan E. (2010). A novel mechanism of sequestering fibroblast growth factor 2 by glypican in lipid rafts, allowing skeletal muscle differentiation. Mol Cell Biol., 30(7), 1634–49.
PMid:20100867 PMCid:PMC2838066
Heinke J, Patterson C, Moser M. (2012). Life is a pattern: vascular assembly within the embryo. Front Biosci, 4, 2269–88.
Hirota K, Semenza GL. (2006). Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Rev OncolHematol., 59(1), 15–26.
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. (2004). Vascular endothelial growth factor and angiogenesis. Pharmacol Rev., 56(4), 549–80.
Kanthou C, Tozer GM. (2009). Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies. Int J ExpPathol., 90(3), 284–94.
Kerbel RS, Kamen BA. (2004). The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer, 4(6), 423–36.
Kerbel RS. (2000). Tumor angiogenesis: past, present and the near future. Carcinogenesis. 21(3), 505–15.
Kerbel RS. (2000). Tumor angiogenesis: past, present and the near future. Carcinogenesis, 21(3), 505–15.
Khan N, Mukhtar H. (2010). Cancer and metastasis: prevention and treatment by green tea. Cancer Metastasis Rev., 29(3), 435–45.
PMid:20714789 PMCid:PMC3142888
Kizaka-Kondoh S, Inoue M, Harada H, Hiraoka M. (2003). Tumor hypoxia: A target for selective cancer therapy. Cancer Sci., 94(12), 1021–8.
List AF. (2001). Vascular Endothelial Growth Factor Signaling Pathway as an Emerging Target in Hematologic Malignancies. Oncologist, 6(90005), 24–31.
Loges S, Schmidt T, Carmeliet P. (2010). Mechanisms of resistance to anti-angiogenic therapy and development of third-generation anti-angiogenic drug candidates. Genes Cancer, 1(1), 12–25.
PMid:21779425 PMCid:PMC3092176
Ma J, Waxman DJ. Combination of antiangiogenesis with chemotherapy for more effective cancer treatment. Mol Cancer Ther. 2008 Dec;7(12):3670–84.
PMid:19074844 PMCid:PMC2637411
Maiti R. (2014). Metronomic chemotherapy. J Pharmacol Pharmacother., 5(3), 186.
PMid:25210398 PMCid:PMC4156829
Mangi MH, Newland AC. (2008). Angiogenesis and Angiogenic Mediators In Haematology Malignancies. Br J Haematol., 111(1), 43–51.
Manjamalai A, Grace, B. (2013). Chemotherapeutic Effect of Essential Oil of Wedeliachinensis (Osbeck) on Inducing Apoptosis, Suppressing Angiogenesis and Lung Metastasis in C57BL/6 Mice Model. J Cancer SciTher., 5, 271-281.
McMahon G. (2000). VEGF Receptor Signaling in Tumor Angiogenesis. Oncologist, 5(90001), 3–10.
Moroney JW, Sood AK, Coleman RL. (2009). Aflibercept in epithelial ovarian carcinoma. Future Oncol., 5(5), 591–600.
PMid:19519199 PMCid:PMC2744352
Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. (1999). Vascular endothelial growth factor (VEGF) and its receptors. FASEB J., 13(1), 9–22.
Nicosia RF. (1998). What is the role of vascular endothelial growth factor-related molecules in tumor angiogenesis? Am J Pathol., 153 (1), 11–6.
Nielsen T, Wittenborn T, Horsman MR. (2012). Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) in Preclinical Studies of Antivascular Treatments. Pharmaceutics, 4(4), 563–89.
PMid:24300371 PMCid:PMC3834929
Owen JL, Mohamadzadeh M. (2013). Macrophages and chemokines as mediators of angiogenesis. Front Physiol. Frontiers, 4, 159.
Raga DD, Alimboyoguen AB, Shen C-C, Herrera AA, Ragasa CY. (2011). Triterpenoids and an Anti-Angiogenic Sterol from Ardisiapyramidalis (Cav.) Pers. The Philippine Agricultural Scientist.
Reinhart-King C. (2012). Mechanical and Chemical Signaling in Angiogenesis. Springer Science & Business Media.
Ria R, Roccaro AM, Merchionne F, Vacca A, Dammacco F, Ribatti D. (2003). Vascular endothelial growth factor and its receptors in multiple myeloma. Leukemia, 17(10), 1961–6.
Ribatti D, Crivellato E. (2012). "Sprouting angiogenesis", a reappraisal. Dev Biol., 372(2), 157–65.
Risinger AL, Giles FJ, Mooberry SL. (2009). Microtubule dynamics as a target in oncology. Cancer Treat Rev., 35(3), 255–61.
PMid:19117686 PMCid:PMC2778221
Sang QX. (1998). Complex role of matrix metalloproteinases in angiogenesis. Cell Res. Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 8(3), 171–7.
Saraswati S, Kanaujia PK, Kumar S, Kumar R, Alhaider AA. (2013). Tylophorine, a phenanthraindolizidine alkaloid isolated from Tylophoraindica exerts antiangiogenic and antitumor activity by targeting vascular endothelial growth factor receptor 2mediated angiogenesis. Mol Cancer., 12(1), 82.
PMid:23895055 PMCid:PMC3733984
Semeraro F, Morescalchi F, Duse S, Parmeggiani F, Gambicorti E, Costagliola C. (2013). Aflibercept in wet AMD: specific role and optimal use. Drug Des DevelTher., 7, 711–22.
Staton CA, Stribbling SM, Tazzyman S, Hughes R, Brown NJ, Lewis CE. (2004). Current methods for assaying angiogenesis in vitro and in vivo. Int J ExpPathol., 85(5), 233–48.
Stenmark KR, Fagan KA, Frid MG. (2006). Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res., 99(7), 675–91.
Sureram S, Senadeera SPD, Hongmanee P, Mahidol C, Ruchirawat S, Kittakoop P. (2012). Antimycobacterial activity of bisbenzylisoquinoline alkaloids from Tiliacoratriandra against multidrug-resistant isolates of Mycobacterium tuberculosis. Bioorg Med ChemLett., 22(8), 2902–5.
Tonnesen MG, Feng X, Clark RA. Angiogenesis in wound healing. J InvestigDermatolSymp Proc., 5(1), 40–6.
Ucuzian AA, Gassman AA, East AT, Greisler HP. (2010). Molecular mediators of angiogenesis. J Burn Care Res., 31(1), 158–75.
PMid:20061852 PMCid:PMC2818794
Vacca A, Ribatti D, Roccaro AM, Frigeri A, Dammacco F. (2001). Bone marrow angiogenesis in patients with active multiple myeloma. SeminOncol., 28(6), 543–50.
Vaupel P. (2004). The role of hypoxia-induced factors in tumor progression. Oncologist, 5, 10–7.
Verheul HM, Pinedo HM. (2000). The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis and early clinical development of VEGF-receptor kinase inhibitors. Clin Breast Cancer. 1, S80–4.
Voelkel NF, Rounds sharon. (2009). The Pulmonary Endothelium: Function in Health and Disease.
Wang X, Abraham S, McKenzie JAG, Jeffs N, Swire M, Tripathi VB, et al. (2013). LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling. Nature, 499(7458), 306–11.
PMid:23868260 PMCid:PMC3836402
Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J. (1993). Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol., 143(2), 401–9.
PMid:7688183 PMCid:PMC1887042
Weston BS. (2003). CTGF Mediates TGF- -Induced Fibronectin Matrix Deposition by UpregulatingActive 5 1 Integrin in Human Mesangial Cells. J Am SocNephrol., 14(3), 601–10.
Yano S, Nishioka Y, Goto H, Sone S. (2003). Molecular mechanisms of angiogenesis in nonsmall cell lung cancer, and therapeutics targeting related molecules. Cancer Sci., 94(6), 479–85.
Yoshida S, Ono M, Shono T, Izumi H, Ishibashi T, Suzuki H, et al. (1997). Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol Cell Biol., 17(7), 4015–23.
PMid:9199336 PMCid:PMC232254
Yuan HT, Khankin E V, Karumanchi SA, Parikh SM. (2009). Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium. Mol Cell Biol., 29(8), 2011–22.
PMid:19223473 PMCid:PMC2663314
Zou H, Otani A, Oishi A, Yodoi Y, Kameda T, Kojima H, et al. (2010). Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice. BiochemBiophys Res Commun., 391(2), 1268–73.

Committee on Publication Ethics

Full Text
Export Citation

View Dimensions

View Plumx

View Altmetric