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Role of the Nervous System in Tumor Angiogenesis

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Cancer Microenvironment

Abstract

The development of cancer involves an intricate process, wherein many identified and unidentified factors play a role. Tumor angiogenesis, growth of new blood vessels, is one of the major prerequisites for tumor growth as tumor cells rely on adequate oxygen and nutrient supply as well as the removal of waste products. Growth factors including VEGF orchestrate the development of angiogenesis. In addition, nervous system via the release of neurotransmitters contributes to tumor angiogenesis. The nervous system governs functional activities of many organs, and, as tumors are not independent organs within an organism, this system is integrally involved in tumor growth and progression via regulating tumor angiogenesis. Various neurotransmitters have been reported to play an important role in tumor angiogenesis.

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. Zhao Y, Adjei AA (2015) Targeting angiogenesis in cancer therapy: moving beyond vascular endothelial growth factor. Oncologist 20(6):660–673

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Nishida N, Yano H, Nishida T, Kamura T, Kojiro M (2006) Angiogenesis in cancer. Vasc Health Risk Manag 2(3):213–219

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. McMahon G (2000) VEGF receptor signaling in tumor angiogenesis. Oncologist 5(Supplement 1):3–10

    Article  PubMed  CAS  Google Scholar 

  5. Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, Jain RK (2011) Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev 91(3):1071–1121

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Zibara K, Awada Z, Dib L, El-Saghir J, Al-Ghadban S, Ibrik A, El-Zein N, El-Sabban M (2015) Anti-angiogenesis therapy and gap junction inhibition reduce MDA-MB-231 breast cancer cell invasion and metastasis in vitro and in vivo. Sci Rep 5:12598

  7. Rusckowski M, Wang Y, Blankenberg FG, Levashova Z, Backer MV, Backer JM (2016) Targeted scVEGF/177Lu radiopharmaceutical inhibits growth of metastases and can be effectively combined with chemotherapy. EJNMMI Res 6(1):1–9

    Article  CAS  Google Scholar 

  8. Vasudev NS, Reynolds AR (2014) Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis 17(3):471–494

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19(11):1423–1437

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Gupta GP, Massagué J (2006) Cancer Metastasis: building a framework. Cell 127(4):679–695

    Article  PubMed  CAS  Google Scholar 

  11. Place AE, Jin Huh S, Polyak K (2011) The microenvironment in breast cancer progression: biology and implications for treatment. Breast Cancer Res 13(6):227

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Weis SM, Cheresh DA (2011) Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med 17(11):1359–1370

    Article  PubMed  CAS  Google Scholar 

  13. Jobling P, Pundavela J, Oliveira SM, Roselli S, Walker MM, Hondermarck H (2015) Nerve–cancer cell cross-talk: a novel promoter of tumor progression. Cancer Res 75(9):1777–1781

    Article  PubMed  CAS  Google Scholar 

  14. Ondicova K, Mravec B (2010) Role of nervous system in cancer aetiopathogenesis. Lancet Oncol 11(6):596–601

    Article  PubMed  Google Scholar 

  15. Chen H, Liu D, Yang Z, Sun L, Deng Q, Yang S, Qian L, Guo L, Yu M, Hu M, Shi M, Guo N (2014) Adrenergic signaling promotes angiogenesis through endothelial cell-tumor cell crosstalk. Endocr Relat Cancer 21(5):783–795

    Article  PubMed  CAS  Google Scholar 

  16. Liu J, Deng G-H, Zhang J, Wang Y, Xia X-Y, Luo X-M, Deng Y-T, He S-S, Mao Y-Y, Peng X-C (2015) The effect of chronic stress on anti-angiogenesis of sunitinib in colorectal cancer models. Psychoneuroendocrinology 52:130–142

    Article  PubMed  CAS  Google Scholar 

  17. Deng G-H, Liu J, Zhang J, Wang Y, Peng X-C, Wei Y-Q, Jiang Y (2014) Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer model. J Exp Clin Cancer Res 33(1):1–12

    Article  CAS  Google Scholar 

  18. Moreno-Smith M, Lee SJ, Lu C, Nagaraja AS, He G, Rupaimoole R, Han HD, Jennings NB, Roh J-W, Nishimura M (2013) Biologic effects of dopamine on tumor vasculature in ovarian carcinoma. Neoplasia 15(5):502–IN515

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Moreno-Smith M, Lu C, Shahzad MM, Pena GNA, Allen JK, Stone RL, Mangala LS, Han HD, Kim HS, Farley D (2011) Dopamine blocks stress-mediated ovarian carcinoma growth. Clin Cancer Res 17(11):3649–3659

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Chakroborty D, Sarkar C, Mitra RB, Banerjee S, Dasgupta PS, Basu S (2004) Depleted dopamine in gastric cancer tissues: dopamine treatment retards growth of gastric cancer by inhibiting angiogenesis. Clin Cancer Res 10(13):4349–4356

    Article  PubMed  CAS  Google Scholar 

  21. Hoeppner LH, Wang Y, Sharma A, Javeed N, Van Keulen VP, Wang E, Yang P, Roden AC, Peikert T, Molina JR (2015) Dopamine D2 receptor agonists inhibit lung cancer progression by reducing angiogenesis and tumor infiltrating myeloid derived suppressor cells. Mol Oncol 9(1):270–281

    Article  PubMed  CAS  Google Scholar 

  22. Fava G, Marucci L, Glaser S, Francis H, De Morrow S, Benedetti A, Alvaro D, Venter J, Meininger C, Patel T (2005) γ-aminobutyric acid inhibits cholangiocarcinoma growth by cyclic AMP–dependent regulation of the protein kinase a/extracellular signal-regulated kinase 1/2 pathway. Cancer Res 65(24):11437–11446

    Article  PubMed  CAS  Google Scholar 

  23. Park SH, Kim B-R, Lee JH, Park ST, Lee S-H, Dong SM, Rho SB (2014) GABARBP down-regulates HIF-1α expression through the VEGFR-2 and PI3K/mTOR/4E-BP1 pathways. Cell Signal 26(7):1506–1513

    Article  PubMed  CAS  Google Scholar 

  24. Nocito A, Dahm F, Jochum W, Jang JH, Georgiev P, Bader M, Graf R, Clavien P-A (2008) Serotonin regulates macrophage-mediated angiogenesis in a mouse model of colon cancer allografts. Cancer Res 68(13):5152–5158

    Article  PubMed  CAS  Google Scholar 

  25. Speyer CL, Hachem AH, Assi A, DeVries JA, Gorski DH (2013) Metabotropic glutamate receptor-1 as a novel target for the anti-angiogenic treatment of breast cancer. Cancer Res 73(8 Supplement):3895

    Article  Google Scholar 

  26. Wen Y, Li J, Koo J, Shin SS, Lin Y, Jeong BS, Mehnert JM, Chen S, Cohen-Sola KA, Goydos JS (2014) Activation of the glutamate receptor GRM1 enhances angiogenic signaling to drive melanoma progression. Cancer Res 74(9):2499–2509

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Zhang Q, Tang X, Zhang Z-F, Velikina R, Shi S, Le AD (2007) Nicotine induces hypoxia-inducible factor-1α expression in human lung cancer cells via nicotinic acetylcholine receptor–mediated signaling pathways. Clin Cancer Res 13(16):4686–4694

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Wong HPS, Yu L, Lam EKY, Tai EKK, Wu WKK, Cho C-H (2007) Nicotine promotes colon tumor growth and angiogenesis through β-adrenergic activation. Toxicol Sci 97(2):279–287

    Article  PubMed  CAS  Google Scholar 

  29. Lombardi Mí G, Negroni M, Pelegrina LT, Castro Mí E, Fiszman GL, Azar Mí E, Morgado CC, Sales Mí E (2013) Autoantibodies against muscarinic receptors in breast cancer: their role in tumor angiogenesis. PLoS One 8(2):e57572

    Article  CAS  Google Scholar 

  30. de la Torre E, Davel L, Jasnis MA, Gotoh T, de Lustig ES, Sales ME (2005) Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice. Breast Cancer Res 7(3):R345–R352

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Medeiros PJ, Jackson DN (2013) Neuropeptide Y Y5-receptor activation on breast cancer cells acts as a paracrine system that stimulates VEGF expression and secretion to promote angiogenesis. Peptides 48:106–113

    Article  PubMed  CAS  Google Scholar 

  32. Medeiros PJ, Al-Khazraji BK, Novielli NM, Postovit LM, Chambers AF, Jackson DN, Neuropeptide Y (2012) Stimulates proliferation and migration in the 4T1 breast cancer cell line. Int J Cancer J Int du Cancer 131(2):276–286

    Article  CAS  Google Scholar 

  33. Alasvand M, Rashidi B, Javanmard SH, Akhavan MM, Khazaei M (2015) Effect of blocking of neuropeptide Y Y2 receptor on tumor angiogenesis and progression in normal and diet-induced obese C57BL/6 mice. Glob J Health Sci 7(7):46883

    Article  Google Scholar 

  34. Lu C, Everhart L, Tilan J, Kuo L, Sun CJ, Munivenkatappa RB, Jönsson-Rylander A-C, Sun J, Kuan-Celarier A, Li L (2010) Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma therapy. Oncogene 29(41):5630–5642

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Nakamura Y, Yasuoka H, Tsujimoto M, Yoshidome K, Nakahara M, Nakao K, Nakamura M, Kakudo K (2006) Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis. Clin Cancer Res 12(4):1201–1207

    Article  PubMed  CAS  Google Scholar 

  36. Nomelini RS, Ribeiro LCDA, Tavares-Murta BM, Adad SJ, Murta EFC (2009) Production of nitric oxide and expression of inducible nitric oxide synthase in ovarian cystic tumors. Mediators Inflamm 2008:186584

  37. Wang L, Shi GG, Yao JC, Gong W, Wei D, Wu TT, Ajani JA, Huang S, Xie K (2005) Expression of endothelial nitric oxide synthase correlates with the angiogenic phenotype of and predicts poor prognosis in human gastric cancer. Gastric Cancer 8(1):18–28

    Article  PubMed  CAS  Google Scholar 

  38. Sarkar C, Chakroborty D, Basu S (2013) Neurotransmitters as regulators of tumor angiogenesis and immunity: the role of catecholamines. J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol 8(1):7–14

    Article  Google Scholar 

  39. Chakroborty D, Sarkar C, Basu B, Dasgupta PS, Basu S (2009) Catecholamines regulate tumor angiogenesis. Cancer Res 69(9):3727–3730

    Article  PubMed  CAS  Google Scholar 

  40. Thaker PH, Han LY, Kamat AA, Arevalo JM, Takahashi R, Lu C, Jennings NB, Armaiz-Pena G, Bankson JA, Ravoori M (2006) Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med 12(8):939–944

    Article  PubMed  CAS  Google Scholar 

  41. Xie H, Li C, He Y, Griffin R, Ye Q, Li L (2015) Chronic stress promotes oral cancer growth and angiogenesis with increased circulating catecholamine and glucocorticoid levels in a mouse model. Oral Oncol 51(11):991–997

    Article  PubMed  CAS  Google Scholar 

  42. Sloan EK, Priceman SJ, Cox BF, Yu S, Pimentel MA, Tangkanangnukul V, Arevalo JM, Morizono K, Karanikolas BD, Wu L (2010) The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res 70(18):7042–7052

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Madden KS, Szpunar MJ, Brown EB (2011) Beta-adrenergic receptors (beta-AR) regulate VEGF and IL-6 production by divergent pathways in high beta-AR-expressing breast cancer cell lines. Breast Cancer Res Treat 130(3):747–758

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, Lockwood G, Egan SE (2005) High-level coexpression of Jag1 and Notch1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res 65(18):8530–8537

    Article  PubMed  CAS  Google Scholar 

  45. Dickson BC, Mulligan AM, Zhang H, Lockwood G, O'Malley FP, Egan SE, Reedijk M (2007) High-level JAG1 mRNA and protein predict poor outcome in breast cancer. Mod Pathol 20(6):685–693

    Article  PubMed  CAS  Google Scholar 

  46. Basu S, Nagy JA, Pal S, Vasile E, Eckelhoefer IA, Bliss VS, Manseau EJ, Dasgupta PS, Dvorak HF, Mukhopadhyay D (2001) The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor. Nat Med 7(5):569–574

    Article  PubMed  CAS  Google Scholar 

  47. Tilan J, Kitlinska J (2010) Sympathetic neurotransmitters and tumor angiogenesis-link between stress and cancer progression. J Oncol 2010:539706

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Sarkar C, Chakroborty D, Chowdhury UR, Dasgupta PS, Basu S (2008) Dopamine increases the efficacy of anticancer drugs in breast and colon cancer preclinical models. Clin Cancer Res 14(8):2502–2510

    Article  PubMed  CAS  Google Scholar 

  49. Schuller HM (2009) Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nat Rev Cancer 9(3):195–205

    Article  PubMed  CAS  Google Scholar 

  50. Egleton RD, Brown KC, Dasgupta P (2009) Angiogenic activity of nicotinic acetylcholine receptors: implications in tobacco-related vascular diseases. Pharmacol Ther 121(2):205–223

    Article  PubMed  CAS  Google Scholar 

  51. Cucina A, Sapienza P, Corvino V, Borrelli V, Mariani V, Randone B, Santoro D'Angelo L, Cavallaro A (2000) Nicotine-induced smooth muscle cell proliferation is mediated through bFGF and TGF-beta 1. Surgery 127(3):316–322

    Article  PubMed  CAS  Google Scholar 

  52. Conklin BS, Zhao W, Zhong DS, Chen C (2002) Nicotine and cotinine up-regulate vascular endothelial growth factor expression in endothelial cells. Am J Pathol 160(2):413–418

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Brown KC, Lau JK, Dom AM, Witte TR, Luo H, Crabtree CM, Shah YH, Shiflett BS, Marcelo AJ, Proper NA, Hardman WE, Egleton RD, Chen YC, Mangiarua EI, Dasgupta P (2012) MG624, an alpha7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway. Angiogenesis 15(1):99–114

    Article  PubMed  CAS  Google Scholar 

  54. Davis R, Rizwani W, Banerjee S, Kovacs M, Haura E, Coppola D, Chellappan S (2009) Nicotine promotes tumor growth and metastasis in mouse models of lung cancer. PLoS One 4(10):e7524

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Lee CH, Huang CS, Chen CS, Tu SH, Wang YJ, Chang YJ, Tam KW, Wei PL, Cheng TC, Chu JS, Chen LC, Wu CH, Ho YS (2010) Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells. J Natl Cancer Inst 102(17):1322–1335

    Article  PubMed  CAS  Google Scholar 

  56. Wu C-H, Lee C-H, Ho Y-S (2011) Nicotinic acetylcholine receptor-based blockade: applications of molecular targets for cancer therapy. Clin Cancer Res 17(11):3533–3541

    Article  PubMed  CAS  Google Scholar 

  57. Dasgupta P, Chellappan SP (2006) Nicotine-mediated cell proliferation and angiogenesis: new twists to an old story. Cell Cycle 5(20):2324–2328

    Article  PubMed  CAS  Google Scholar 

  58. Fiszman GL, Middonno MC, de la Torre E, Farina M, Español AJ, Sales ME (2007) Activation of muscarinic cholinergic receptors induces MCF-7 cells proliferation and angiogenesis by stimulating nitric oxide synthase activity. Cancer Biol Ther 6(7):1106–1113

    Article  PubMed  CAS  Google Scholar 

  59. Li L, Kilbourn RG, Adams J, Fidler IJ (1991) Role of nitric oxide in lysis of tumor cells by cytokine-activated endothelial cells. Cancer Res 51(10):2531–2535

    PubMed  CAS  Google Scholar 

  60. Cianchi F, Cortesini C, Fantappiè O, Messerini L, Schiavone N, Vannacci A, Nistri S, Sardi I, Baroni G, Marzocca C, Perna F, Mazzanti R, Bechi P, Masini E (2003) Inducible nitric oxide synthase expression in human colorectal cancer: correlation with tumor angiogenesis. Am J Pathol 162(3):793–801

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Fukumura D, Kashiwagi S, Jain RK (2006) The role of nitric oxide in tumour progression. Nat Rev Cancer 6(7):521–534

    Article  PubMed  CAS  Google Scholar 

  62. Ridnour LA, Thomas DD, Donzelli S, Espey MG, Roberts DD, Wink DA, Isenberg JS (2006) The biphasic nature of nitric oxide responses in tumor biology. Antioxid Redox Signal 8(7–8):1329–1337

    Article  PubMed  CAS  Google Scholar 

  63. Andrade SP, Hart IR, Piper PJ (1992) Inhibitors of nitric oxide synthase selectively reduce flow in tumour-associated neovasculature. Br J Pharmacol 107(4):1092–1095

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Chu SC, Marks-Konczalik J, Wu H-P, Banks TC, Moss J (1998) Analysis of the cytokine-stimulated human inducible nitric oxide synthase (iNOS) gene: characterization of differences between human and mouse iNOS promoters. Biochem Biophys Res Commun 248(3):871–878

    Article  PubMed  CAS  Google Scholar 

  65. Vahora H, Khan MA, Alalami U, Hussain A (2016) The potential role of nitric oxide in halting cancer progression through chemoprevention. J Cancer Prev 21(1):1–12

    Article  PubMed  PubMed Central  Google Scholar 

  66. Radisky ES, Radisky DC (2015) Matrix metalloproteinases as breast cancer drivers and therapeutic targets. Front Biosci (Landmark ed) 20:1144–1163

    Article  CAS  Google Scholar 

  67. Wangari-Talbot J, Wall BA, Goydos JS, Chen S (2012) Functional effects of GRM1 suppression in human melanoma cells. Mol Cancer Res 10(11):1440–1450

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Xia H, Zhao YN, Yu CH, Zhao YL, Liu Y (2016) Inhibition of metabotropic glutamate receptor 1 suppresses tumor growth and angiogenesis in experimental non-small cell lung cancer. Eur J Pharmacol 783:103–111

    Article  PubMed  CAS  Google Scholar 

  69. He T, Qi F, Jia L, Wang S, Wang C, Song N, Fu Y, Li L, Luo Y (2015) Tumor cell-secreted angiogenin induces angiogenic activity of endothelial cells by suppressing miR-542-3p. Cancer Lett 368(1):115–125

    Article  PubMed  CAS  Google Scholar 

  70. Miyake M, Goodison S, Lawton A, Gomes-Giacoia E, Rosser C (2015) Angiogenin promotes tumoral growth and angiogenesis by regulating matrix metallopeptidase-2 expression via the ERK1/2 pathway. Oncogene 34(7):890–901

    Article  PubMed  CAS  Google Scholar 

  71. Shu J, Huang M, Tian Q, Shui Q, Zhou Y, Chen J (2015) Downregulation of angiogenin inhibits the growth and induces apoptosis in human bladder cancer cells through regulating AKT/mTOR signaling pathway. J Mol Histol 46(2):157–171

    Article  PubMed  CAS  Google Scholar 

  72. Sasi SP, Yan X, Enderling H, Park D, Gilbert H-Y, Curry C, Coleman C, Hlatky L, Qin G, Kishore R (2012) Breaking the ‘harmony’of TNF-α signaling for cancer treatment. Oncogene 31(37):4117–4127

    Article  PubMed  CAS  Google Scholar 

  73. Geng L, Chaudhuri A, Talmon G, Wisecarver JL, Wang J (2013) TGF-Beta suppresses VEGFA-mediated angiogenesis in colon cancer metastasis. PLoS One 8(3):e59918

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Lin C-Y, Hung S-Y, Chen H-T, Tsou H-K, Fong Y-C, Wang S-W, Tang C-H (2014) Brain-derived neurotrophic factor increases vascular endothelial growth factor expression and enhances angiogenesis in human chondrosarcoma cells. Biochem Pharmacol 91(4):522–533

    Article  PubMed  CAS  Google Scholar 

  75. Larrieu-Lahargue F, Welm AL, Bouchecareilh M, Alitalo K, Li DY, Bikfalvi A, Auguste P (2012) Blocking fibroblast growth factor receptor signaling inhibits tumor growth, lymphangiogenesis, and metastasis. PLoS One 7(6):e39540

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Wang W-M, Zhao Z-L, Ma S-R, Yu G-T, Liu B, Zhang L, Zhang W-F, Kulkarni AB, Sun Z-J, Zhao Y-F (2015) Epidermal growth factor receptor inhibition reduces angiogenesis via hypoxia-inducible factor-1α and notch1 in head neck squamous cell carcinoma. PLoS One 10(2):e0119723

  77. Romon R, Adriaenssens E, Lagadec C, Germain E, Hondermarck H, Le Bourhis X (2010) Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways. Breast Cancer 9:11

    Google Scholar 

  78. Ren Y, Cao B, Law S, Xie Y, Lee PY, Cheung L, Chen Y, Huang X, Chan HM, Zhao P (2005) Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res 11(17):6190–6197

    Article  PubMed  CAS  Google Scholar 

  79. Sugie S, Mukai S, Yamasaki K, Kamibeppu T, Tsukino H, Kamoto T (2016) Plasma macrophage-stimulating protein and hepatocyte growth factor levels are associated with prostate cancer progression. Hum Cell 29(1):22–29

    Article  PubMed  CAS  Google Scholar 

  80. Walsh EM, Kim R, Del Valle L, Weaver M, Sheffield J, Lazarovici P, Marcinkiewicz C (2012) Importance of interaction between nerve growth factor and α9β1 integrin in glial tumor angiogenesis. Neuro-Oncology 14(7):890–901

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Staniszewska I, Zaveri S, Del Valle L, Oliva I, Rothman VL, Croul SE, Roberts DD, Mosher DF, Tuszynski GP, Marcinkiewicz C (2007) Interaction of α9β1 integrin with thrombospondin-1 promotes angiogenesis. Circ Res 100(9):1308–1316

    Article  PubMed  CAS  Google Scholar 

  82. Vlahakis NE, Young BA, Atakilit A, Hawkridge AE, Issaka RB, Boudreau N, Sheppard D (2007) Integrin α9β1 directly binds to vascular endothelial growth factor (VEGF)-a and contributes to VEGF-A-induced angiogenesis. J Biol Chem 282(20):15187–15196

    Article  PubMed  CAS  Google Scholar 

  83. Staniszewska I, Sariyer IK, Lecht S, Brown MC, Walsh EM, Tuszynski GP, Safak M, Lazarovici P, Marcinkiewicz C (2008) Integrin α9β1 is a receptor for nerve growth factor and other neurotrophins. J Cell Sci 121(4):504–513

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Nilsson UW, Abrahamsson A, Dabrosin C (2010) Angiogenin regulation by estradiol in breast tissue: tamoxifen inhibits angiogenin nuclear translocation and antiangiogenin therapy reduces breast cancer growth in vivo. Clin Cancer Res 16(14):3659–3669

    Article  PubMed  CAS  Google Scholar 

  85. Katona TM, Neubauer BL, Iversen PW, Zhang S, Baldridge LA, Cheng L (2005) Elevated expression of angiogenin in prostate cancer and its precursors. Clin Cancer Res 11(23):8358–8363

    Article  PubMed  CAS  Google Scholar 

  86. Hisai H, Kato J, Kobune M, Murakami T, Miyanishi K, Takahashi M, Yoshizaki N, Takimoto R, Terui T, Niitsu Y (2003) Increased expression of angiogenin in hepatocellular carcinoma in correlation with tumor vascularity. Clin Cancer Res 9(13):4852–4859

    PubMed  CAS  Google Scholar 

  87. Miyake H, Hara I, Yamanaka K, Gohji K, Arakawa S, Kamidono S (1999) Increased angiogenin expression in the tumor tissue and serum of urothelial carcinoma patients is related to disease progression and recurrence. Cancer 86(2):316–324

    Article  PubMed  CAS  Google Scholar 

  88. Gao X, Xu Z (2008) Mechanisms of action of angiogenin. Acta Biochim Biophys Sin 40(7):619–624

    Article  PubMed  CAS  Google Scholar 

  89. de Aguiar RB, Parise CB, Souza CRT, Braggion C, Quintilio W, Moro AM, Navarro Marques FL, Buchpiguel CA, Chammas R, de Moraes JZ (2016) Blocking FGF2 with a new specific monoclonal antibody impairs angiogenesis and experimental metastatic melanoma, suggesting a potential role in adjuvant settings. Cancer Lett 371(2):151–160

    Article  PubMed  CAS  Google Scholar 

  90. Lai KC, Liu CJ, Lin TJ, Mar AC, Wang HH, Chen CW, Hong ZX, Lee TC (2016) Blocking TNF-alpha inhibits angiogenesis and growth of IFIT2-depleted metastatic oral squamous cell carcinoma cells. Cancer Lett 370(2):207–215

    Article  PubMed  CAS  Google Scholar 

  91. Kawaguchi M, Kataoka H (2014) Mechanisms of hepatocyte growth factor activation in cancer tissues. Cancers 6(4):1890–1904

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Kataoka H, Miyata S, Uchinokura S, Itoh H (2003) Roles of hepatocyte growth factor (HGF) activator and HGF activator inhibitor in the pericellular activation of HGF/scatter factor. Cancer Metastasis Rev 22(2–3):223–236

    Article  PubMed  CAS  Google Scholar 

  93. Ellis LM (2006) The role of neuropilins in cancer. Mol Cancer Ther 5(5):1099–1107

    Article  PubMed  CAS  Google Scholar 

  94. Djordjevic S, Driscoll PC (2013) Targeting VEGF signalling via the neuropilin co-receptor. Drug Discov Today 18(9–10):447–455

    Article  PubMed  CAS  Google Scholar 

  95. Li L, Jiang X, Zhang Q, Dong X, Gao Y, He Y, Qiao H, Xie F, Xie X, Sun X (2016) Neuropilin-1 is associated with clinicopathology of gastric cancer and contributes to cell proliferation and migration as multifunctional co-receptors. J Exp Clin Cancer Res 35(1):16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

NK was supported by an Australian Postgraduate Research Award, LS and KN was supported by the College of Heath and Biomedicine Victoria University, Australia and VA was supported by the Centre for Chronic Disease, Victoria University, Australia.

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Kuol, N., Stojanovska, L., Apostolopoulos, V. et al. Role of the Nervous System in Tumor Angiogenesis. Cancer Microenvironment 11, 1–11 (2018). https://doi.org/10.1007/s12307-018-0207-3

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