Neuropeptides and Angiogenesis

Chapter
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 6)

Abstract

Neuropeptides are one of the most conserved proteins across different species and are ubiquitously expressed in different organs. In the peripheral nervous system, neuropeptides are secreted by the sensory and autonomic nerves and participate in a wide range of functions including immune surveillance, cardiovascular homeostasis, regulation of endocrine function, cytokine and growth factor release, and importantly angiogenesis. Neuropeptides including neuropeptide Y, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and somatostatin (SS) are some of the neuropeptides that have been investigated regarding their role in modulating the vascular system and angiogenesis. All of these neuropeptides are pro-angiogenic except SS, which has anti-­angiogenic properties. This chapter aims to present up-to-date evidence on the various mechanisms of action of the aforementioned neuropeptides and their clinical implications.

Keywords

Neuropeptides Wound healing Cancer Ischemia 

References

  1. 1.
    Hulagu S, Senturk O, Erdem A et al (2002) Effects of losartan, somatostatin and losartan plus somatostatin on portal hemodynamics and renal functions in cirrhosis. Hepatogastroenterology 49:783–787PubMedGoogle Scholar
  2. 2.
    Ruohonen ST, Abe K, Kero M et al (2009) Sympathetic nervous system-targeted neuropeptide Y overexpression in mice enhances neointimal formation in response to vascular injury. Peptides 30:715–720PubMedCrossRefGoogle Scholar
  3. 3.
    Kuo LE, Abe K, Zukowska Z (2007) Stress, NPY and vascular remodeling: implications for stress-related diseases. Peptides 28:435–440PubMedCrossRefGoogle Scholar
  4. 4.
    Abe K, Tilan JU, Zukowska Z (2007) NPY and NPY receptors in vascular remodeling. Curr Top Med Chem 7:1704–1709PubMedCrossRefGoogle Scholar
  5. 5.
    Zukowska Z, Grant DS, Lee EW (2003) Neuropeptide Y: a novel mechanism for ischemic angiogenesis. Trends Cardiovasc Med 13:86–92PubMedCrossRefGoogle Scholar
  6. 6.
    Lee EW, Grant DS, Movafagh S et al (2003) Impaired angiogenesis in neuropeptide Y (NPY)-Y2 receptor knockout mice. Peptides 24:99–106PubMedCrossRefGoogle Scholar
  7. 7.
    Ejaz A, LoGerfo FW, Pradhan L (2011) Diabetic neuropathy and heart failure: role of neuropeptides. Expert Rev Mol Med 13:e26PubMedCrossRefGoogle Scholar
  8. 8.
    Jain M, LoGerfo FW, Guthrie P et al (2011) Effect of hyperglycemia and neuropeptides on interleukin-8 expression and angiogenesis in dermal microvascular endothelial cells. J Vasc Surg 53:1654–1660 e2Google Scholar
  9. 9.
    Pradhan L, Cai X, Wu S et al (2011) Gene expression of pro-inflammatory cytokines and neuropeptides in diabetic wound healing. J Surg Res 167:336–342PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang S, Liu Y, Guo S et al (2010) Vasoactive intestinal polypeptide relaxes isolated rat pulmonary artery rings through two distinct mechanisms. J Physiol Sci 60:389–397PubMedCrossRefGoogle Scholar
  11. 11.
    Blomqvist AG, Herzog H (1997) Y-receptor subtypes—how many more? Trends Neurosci 20:294–298PubMedCrossRefGoogle Scholar
  12. 12.
    Adrian TE, Allen JM, Bloom SR et al (1983) Neuropeptide Y distribution in human brain. Nature 306:584–586PubMedCrossRefGoogle Scholar
  13. 13.
    Fried G, Terenius L, Hokfelt T et al (1985) Evidence for differential localization of noradrenaline and neuropeptide Y in neuronal storage vesicles isolated from rat vas deferens. J Neurosci 5:450–458PubMedGoogle Scholar
  14. 14.
    Ekblad E, Edvinsson L, Wahlestedt C et al (1984) Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers. Regul Pept 8:225–235PubMedCrossRefGoogle Scholar
  15. 15.
    Zukowska Z, Pons J, Lee EW et al (2003) Neuropeptide Y: a new mediator linking sympathetic nerves, blood vessels and immune system? Can J Physiol Pharmacol 81:89–94PubMedCrossRefGoogle Scholar
  16. 16.
    Brothers SP, Wahlestedt C (2010) Therapeutic potential of neuropeptide Y (NPY) receptor ligands. EMBO Mol Med 2:429–439PubMedCrossRefGoogle Scholar
  17. 17.
    Franco-Cereceda A, Lundberg JM, Dahlof C (1985) Neuropeptide Y and sympathetic control of heart contractility and coronary vascular tone. Acta Physiol Scand 124:361–369PubMedCrossRefGoogle Scholar
  18. 18.
    Erlinge D, Brunkwall J, Edvinsson L (1994) Neuropeptide Y stimulates proliferation of human vascular smooth muscle cells: cooperation with noradrenaline and ATP. Regul Pept 50:259–265PubMedCrossRefGoogle Scholar
  19. 19.
    Zukowska-Grojec Z, Pruszczyk P, Colton C et al (1993) Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells. Peptides 14:263–268PubMedCrossRefGoogle Scholar
  20. 20.
    Bedoui S, Kawamura N, Straub RH et al (2003) Relevance of neuropeptide Y for the neuroimmune crosstalk. J Neuroimmunol 134:1–11PubMedCrossRefGoogle Scholar
  21. 21.
    Pedrazzini T, Pralong F, Grouzmann E (2003) Neuropeptide Y: the universal soldier. Cell Mol Life Sci 60:350–377PubMedCrossRefGoogle Scholar
  22. 22.
    Zukowska-Grojec Z, Karwatowska-Prokopczuk E, Rose W et al (1998) Neuropeptide Y: a novel angiogenic factor from the sympathetic nerves and endothelium. Circ Res 83:187–195PubMedCrossRefGoogle Scholar
  23. 23.
    Kohno D, Gao HZ, Muroya S et al (2003) Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin. Diabetes 52:948–956PubMedCrossRefGoogle Scholar
  24. 24.
    Ejaz A, LoGerfo FW, Khabbaz K et al (2011) Expression of neuropeptide Y, substance P, and their receptors in the right atrium of diabetic patients. Clin Transl Sci 4:346–450PubMedCrossRefGoogle Scholar
  25. 25.
    Robich MP, Matyal R, Chu LM et al (2010) Effects of neuropeptide Y on collateral development in a swine model of chronic myocardial ischemia. J Mol Cell Cardiol 49:1022–1030PubMedCrossRefGoogle Scholar
  26. 26.
    Zatelli MC, Minoia M, Martini C et al (2010) Everolimus as a new potential antiproliferative agent in aggressive human bronchial carcinoids. Endocr Relat Cancer 17:719–729PubMedCrossRefGoogle Scholar
  27. 27.
    Lee EW, Michalkiewicz M, Kitlinska J et al (2003) Neuropeptide Y induces ischemic angiogenesis and restores function of ischemic skeletal muscles. J Clin Invest 111:1853–1862PubMedGoogle Scholar
  28. 28.
    Movafagh S, Hobson JP, Spiegel S et al (2006) Neuropeptide Y induces migration, proliferation, and tube formation of endothelial cells bimodally via Y1, Y2, and Y5 receptors. FASEB J 20:1924–1926PubMedCrossRefGoogle Scholar
  29. 29.
    Ackermann PW, Ahmed M, Kreicbergs A (2002) Early nerve regeneration after Achilles tendon rupture—a prerequisite for healing? A study in the rat. J Orthop Res 20:849–856PubMedCrossRefGoogle Scholar
  30. 30.
    Ekstrand AJ, Cao R, Bjorndahl M et al (2003) Deletion of neuropeptide Y (NPY) 2 receptor in mice results in blockage of NPY-induced angiogenesis and delayed wound healing. Proc Natl Acad Sci U S A 100:6033–6038PubMedCrossRefGoogle Scholar
  31. 31.
    Lu C, Everhart L, Tilan J et al (2010) Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma therapy. Oncogene 29:5630–5642PubMedCrossRefGoogle Scholar
  32. 32.
    Lenkinski RE, Bloch BN, Liu F et al (2008) An illustration of the potential for mapping MRI/MRS parameters with genetic over-expression profiles in human prostate cancer. MAGMA 21:411–421PubMedCrossRefGoogle Scholar
  33. 33.
    Kitlinska J, Abe K, Kuo L et al (2005) Differential effects of neuropeptide Y on the growth and vascularization of neural crest-derived tumors. Cancer Res 65:1719–1728PubMedCrossRefGoogle Scholar
  34. 34.
    Hokfelt T, Kellerth JO, Nilsson G et al (1975) Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Res 100:235–252PubMedCrossRefGoogle Scholar
  35. 35.
    Maggi CA (2000) The troubled story of tachykinins and neurokinins. Trends Pharmacol Sci 21:173–175PubMedCrossRefGoogle Scholar
  36. 36.
    Pradhan L, Nabzdyk C, Andersen ND et al (2009) Inflammation and neuropeptides: the connection in diabetic wound healing. Expert Rev Mol Med 11:e2PubMedCrossRefGoogle Scholar
  37. 37.
    Maggi CA (1995) The mammalian tachykinin receptors. Gen Pharmacol 26:911–944PubMedCrossRefGoogle Scholar
  38. 38.
    Nieber K, Oehme P (1982) [Substance P—a neuropeptide transmitter]. Z Gesamte Inn Med 37:577–582PubMedGoogle Scholar
  39. 39.
    Nilsson J, von Euler AM, Dalsgaard CJ (1985) Stimulation of connective tissue cell growth by substance P and substance K. Nature 315:61–63PubMedCrossRefGoogle Scholar
  40. 40.
    Ziche M, Morbidelli L, Pacini M et al (1990) Substance P stimulates neovascularization in vivo and proliferation of cultured endothelial cells. Microvasc Res 40:264–278PubMedCrossRefGoogle Scholar
  41. 41.
    Rameshwar P, Poddar A, Zhu G et al (1997) Receptor induction regulates the synergistic effects of substance P with IL-1 and platelet-derived growth factor on the proliferation of bone marrow fibroblasts. J Immunol 158:3417–3424PubMedGoogle Scholar
  42. 42.
    Khawaja AM, Rogers DF (1996) Tachykinins: receptor to effector. Int J Biochem Cell Biol 28:721–738PubMedCrossRefGoogle Scholar
  43. 43.
    Harrison S, Geppetti P (2001) Substance p. Int J Biochem Cell Biol 33:555–576PubMedCrossRefGoogle Scholar
  44. 44.
    Delgado AV, McManus AT, Chambers JP (2003) Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P. Neuropeptides 37:355–361PubMedCrossRefGoogle Scholar
  45. 45.
    Chu JM, Chen LW, Chan YS et al (2011) Neuroprotective effects of neurokinin receptor one in dopaminergic neurons are mediated through Akt/PKB cell signaling pathway. Neuropharmacology 61:1389–1398PubMedCrossRefGoogle Scholar
  46. 46.
    Bulut K, Felderbauer P, Deters S et al (2008) Sensory neuropeptides and epithelial cell restitution: the relevance of SP- and CGRP-stimulated mast cells. Int J Colorectal Dis 23:535–541PubMedCrossRefGoogle Scholar
  47. 47.
    Felderbauer P, Bulut K, Hoeck K et al (2007) Substance P induces intestinal wound healing via fibroblasts—evidence for a TGF-beta-dependent effect. Int J Colorectal Dis 22:1475–1480PubMedCrossRefGoogle Scholar
  48. 48.
    Couture R, Gaudreau P, St-Pierre S et al (1980) The dog common carotid artery: a sensitive bioassay for studying vasodilator effects of substance P and of kinins. Can J Physiol Pharmacol 58:1234–1244PubMedCrossRefGoogle Scholar
  49. 49.
    Persson MG, Hedqvist P, Gustafsson LE (1991) Nerve-induced tachykinin-mediated vasodilation in skeletal muscle is dependent on nitric oxide formation. Eur J Pharmacol 205:295–301PubMedCrossRefGoogle Scholar
  50. 50.
    Gustafsson LE, Wiklund CU, Wiklund NP et al (1990) Modulation of autonomic neuroeffector transmission by nitric oxide in guinea pig ileum. Biochem Biophys Res Commun 173:106–110PubMedCrossRefGoogle Scholar
  51. 51.
    Amadesi S, Reni C, Katare R et al (2012) Role for substance P-based nociceptive signaling in progenitor cell activation and angiogenesis during ischemia in mice and in human subjects. Circulation 125(14):1774–1786PubMedCrossRefGoogle Scholar
  52. 52.
    Andersson G, Backman LJ, Scott A et al (2011) Substance P accelerates hypercellularity and angiogenesis in tendon tissue and enhances paratendinitis in response to Achilles tendon overuse in a tendinopathy model. Br J Sports Med 45:1017–1022PubMedCrossRefGoogle Scholar
  53. 53.
    Munoz M, Covenas R (2010) Neurokinin-1 receptor: a new promising target in the treatment of cancer. Discov Med 10:305–313PubMedGoogle Scholar
  54. 54.
    Munoz M, Rosso M, Covenas R (2011) The NK-1 receptor: a new target in cancer therapy. Curr Drug Targets 12:909–921PubMedCrossRefGoogle Scholar
  55. 55.
    Wiedermann CJ, Auer B, Sitte B et al (1996) Induction of endothelial cell differentiation into capillary-like structures by substance P. Eur J Pharmacol 298:335–338PubMedCrossRefGoogle Scholar
  56. 56.
    Kohara H, Tajima S, Yamamoto M et al (2010) Angiogenesis induced by controlled release of neuropeptide substance P. Biomaterials 31:8617–8625PubMedCrossRefGoogle Scholar
  57. 57.
    Scott JR, Muangman P, Gibran NS (2007) Making sense of hypertrophic scar: a role for nerves. Wound Repair Regen 15(suppl 1):S27–S31PubMedCrossRefGoogle Scholar
  58. 58.
    Burssens P, Steyaert A, Forsyth R et al (2005) Exogenously administered substance P and neutral endopeptidase inhibitors stimulate fibroblast proliferation, angiogenesis and collagen organization during Achilles tendon healing. Foot Ankle Int 26:832–839PubMedGoogle Scholar
  59. 59.
    Khare VK, Albino AP, Reed JA (1998) The neuropeptide/mast cell secretagogue substance P is expressed in cutaneous melanocytic lesions. J Cutan Pathol 25:2–10PubMedCrossRefGoogle Scholar
  60. 60.
    Singh D, Joshi DD, Hameed M et al (2000) Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis. Proc Natl Acad Sci U S A 97:388–393PubMedCrossRefGoogle Scholar
  61. 61.
    Harford-Wright E, Lewis KM, Vink R (2011) Towards drug discovery for brain tumours: interaction of kinins and tumours at the blood brain barrier interface. Recent Pat CNS Drug Discov 6:31–40PubMedCrossRefGoogle Scholar
  62. 62.
    Munoz M, Covenas R (2011) NK-1 receptor antagonists: a new paradigm in pharmacological therapy. Curr Med Chem 18:1820–1831PubMedCrossRefGoogle Scholar
  63. 63.
    Munoz M, Rosso M, Robles-Frias MJ et al (2010) The NK-1 receptor is expressed in human melanoma and is involved in the antitumor action of the NK-1 receptor antagonist aprepitant on melanoma cell lines. Lab Invest 90:1259–1269PubMedCrossRefGoogle Scholar
  64. 64.
    Mayordomo C, Garcia-Recio S, Ametller E et al (2012) Targeting of substance P induces cancer cell death and decreases the steady state of EGFR and Her2. J Cell Physiol 227:1358–1366PubMedCrossRefGoogle Scholar
  65. 65.
    Adeghate E, Ponery A (2003) Pancreatic peptides, neuropeptides and neurotransmitters in diabetes mellitus: a review. Int J Diabetes Metab 11:1–6Google Scholar
  66. 66.
    Bergdahl A, Valdemarsson S, Nilsson T et al (1999) Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat. Acta Physiol Scand 165:15–23PubMedCrossRefGoogle Scholar
  67. 67.
    McLatchie LM, Fraser NJ, Main MJ et al (1998) RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393:333–339PubMedCrossRefGoogle Scholar
  68. 68.
    van Rossum D, Hanisch UK, Quirion R (1997) Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci Biobehav Rev 21:649–678PubMedCrossRefGoogle Scholar
  69. 69.
    Walker CS, Conner AC, Poyner DR et al (2010) Regulation of signal transduction by calcitonin gene-related peptide receptors. Trends Pharmacol Sci 31:476–483PubMedCrossRefGoogle Scholar
  70. 70.
    Brain SD, Williams TJ, Tippins JR et al (1985) Calcitonin gene-related peptide is a potent vasodilator. Nature 313:54–56PubMedCrossRefGoogle Scholar
  71. 71.
    Gardiner SM, Compton AM, Kemp PA et al (1991) Haemodynamic effects of human alpha-­calcitonin gene-related peptide following administration of endothelin-1 or NG-nitro-L-­arginine methyl ester in conscious rats. Br J Pharmacol 103:1256–1262PubMedCrossRefGoogle Scholar
  72. 72.
    Manek S, Terenghi G, Shurey C et al (1993) Neovascularisation precedes neural changes in the rat groin skin flap following denervation: an immunohistochemical study. Br J Plast Surg 46:48–55PubMedCrossRefGoogle Scholar
  73. 73.
    Manek S, Terenghi G, Shurey C et al (1994) Angiogenesis and reinnervation in skin flaps: the effects of ischaemia examined in an animal model. Int J Exp Pathol 75:243–255PubMedGoogle Scholar
  74. 74.
    Mapp PI, McWilliams DF, Turley MJ et al (2012) A role for the sensory neuropeptide calcitonin gene-related peptide in endothelial cell proliferation in vivo. Br J Pharmacol 166:1261–1271PubMedCrossRefGoogle Scholar
  75. 75.
    Zheng S, Li W, Xu M et al (2010) Calcitonin gene-related peptide promotes angiogenesis via AMP-activated protein kinase. Am J Physiol Cell Physiol 299:C1485–C1492PubMedCrossRefGoogle Scholar
  76. 76.
    Toda M, Suzuki T, Hosono K et al (2008) Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis. Biomed Pharmacother 62:352–359PubMedCrossRefGoogle Scholar
  77. 77.
    Ohno T, Hattori Y, Komine R et al (2008) Roles of calcitonin gene-related peptide in maintenance of gastric mucosal integrity and in enhancement of ulcer healing and angiogenesis. Gastroenterology 134:215–225PubMedCrossRefGoogle Scholar
  78. 78.
    Toda M, Suzuki T, Hosono K et al (2008) Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide. Proc Natl Acad Sci U S A 105:13550–13555PubMedCrossRefGoogle Scholar
  79. 79.
    White CM, Ji S, Cai H et al (2010) Therapeutic potential of vasoactive intestinal peptide and its receptors in neurological disorders. CNS Neurol Disord Drug Targets 9:661–666PubMedCrossRefGoogle Scholar
  80. 80.
    Gaw AJ, Aberdeen J, Humphrey PP et al (1991) Relaxation of sheep cerebral arteries by vasoactive intestinal polypeptide and neurogenic stimulation: inhibition by L-NG-monomethyl arginine in endothelium-denuded vessels. Br J Pharmacol 102:567–572PubMedCrossRefGoogle Scholar
  81. 81.
    Guan CX, Cui YR, Sun GY et al (2009) Role of CREB in vasoactive intestinal peptide-­mediated wound healing in human bronchial epithelial cells. Regul Pept 153:64–69PubMedCrossRefGoogle Scholar
  82. 82.
    Wollina U, Huschenbeck J, Knoll B et al (1997) Vasoactive intestinal peptide supports induced migration of human keratinocytes and their colonization of an artificial polyurethane matrix. Regul Pept 70:29–36PubMedCrossRefGoogle Scholar
  83. 83.
    Wollina U, Knopf B (1993) Vasoactive-intestinal-peptide (vip) modulates early events of migration in human keratinocytes. Int J Oncol 2:229–232PubMedGoogle Scholar
  84. 84.
    Marion-Audibert AM, Nejjari M, Pourreyron C et al (2000) [Effects of endocrine peptides on proliferation, migration and differentiation of human endothelial cells]. Gastroenterol Clin Biol 24:644–648PubMedGoogle Scholar
  85. 85.
    Yang J, Zong CH, Zhao CH et al (2009) [Vasoactive intestinal peptide enhances angiogenesis after focal cerebral ischemia]. Nan Fang Yi Ke Da Xue Xue Bao 29:619–622PubMedGoogle Scholar
  86. 86.
    Yang J, Zong CH, Zhao ZH et al (2009) Vasoactive intestinal peptide in rats with focal cerebral ischemia enhances angiogenesis. Neuroscience 161:413–421PubMedCrossRefGoogle Scholar
  87. 87.
    Zhao Z, Cheng Q, Li X et al (2006) [c-fos antisense oligodeoxynucleotide reduces VIP-­induced upregulation of VEGF expression in small cell lung cancer cells]. Zhongguo Fei Ai Za Zhi 9:312–315PubMedGoogle Scholar
  88. 88.
    Collado B, Carmena MJ, Clemente C et al (2007) Vasoactive intestinal peptide enhances growth and angiogenesis of human experimental prostate cancer in a xenograft model. Peptides 28:1896–1901PubMedCrossRefGoogle Scholar
  89. 89.
    Collado B, Sanchez MG, Diaz-Laviada I et al (2005) Vasoactive intestinal peptide (VIP) induces c-fos expression in LNCaP prostate cancer cells through a mechanism that involves Ca2+ signalling. Implications in angiogenesis and neuroendocrine differentiation. Biochim Biophys Acta 1744:224–233PubMedCrossRefGoogle Scholar
  90. 90.
    Ogasawara M, Murata J, Kamitani Y et al (1999) Inhibition by vasoactive intestinal polypeptide (VIP) of angiogenesis induced by murine colon 26-L5 carcinoma cells metastasized in liver. Clin Exp Metastasis 17:283–291PubMedCrossRefGoogle Scholar
  91. 91.
    Brazeau P, Vale W, Burgus R et al (1974) Isolation of somatostatin (a somatotropin release inhibiting factor) of ovine hypothalamic origin. Can J Biochem 52:1067–1072PubMedCrossRefGoogle Scholar
  92. 92.
    Ferjoux G, Bousquet C, Cordelier P et al (2000) Signal transduction of somatostatin receptors negatively controlling cell proliferation. J Physiol Paris 94:205–210PubMedCrossRefGoogle Scholar
  93. 93.
    Dasgupta P (2004) Somatostatin analogues: multiple roles in cellular proliferation, neoplasia, and angiogenesis. Pharmacol Ther 102:61–85PubMedCrossRefGoogle Scholar
  94. 94.
    Shulkes A (1994) Somatostatin: physiology and clinical applications. Baillieres Clin Endocrinol Metab 8:215–236PubMedCrossRefGoogle Scholar
  95. 95.
    McIntosh CH, Bakich V, Kwok YN et al (1986) A comparison of the inhibitory effects of somatostatin-14, -25, and -28 on motility of the guinea pig ileum. Can J Physiol Pharmacol 64:303–306PubMedCrossRefGoogle Scholar
  96. 96.
    Koch H (1976) [Gastrointestinal hormones and blood circulation in the gastric mucosa]. Z Gastroenterol 14(suppl):105–109PubMedGoogle Scholar
  97. 97.
    Tyden G, Samnegard H, Thulin L et al (1979) Circulatory effects of somatostatin in anesthetized man. Acta Chir Scand 145:443–446PubMedGoogle Scholar
  98. 98.
    Huang HC, Lee FY, Chan CC et al (2002) Effects of somatostatin and octreotide on portal-­systemic collaterals in portal hypertensive rats. J Hepatol 36:163–168PubMedCrossRefGoogle Scholar
  99. 99.
    Woltering EA, Barrie R, O’Dorisio TM et al (1991) Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane. J Surg Res 50:245–251PubMedCrossRefGoogle Scholar
  100. 100.
    Bocci G, Culler MD, Fioravanti A et al (2007) In vitro antiangiogenic activity of selective somatostatin subtype-1 receptor agonists. Eur J Clin Invest 37:700–708PubMedCrossRefGoogle Scholar
  101. 101.
    Dal Monte M, Cammalleri M, Martini D et al (2007) Antiangiogenic role of somatostatin receptor 2 in a model of hypoxia-induced neovascularization in the retina: results from transgenic mice. Invest Ophthalmol Vis Sci 48:3480–3489PubMedCrossRefGoogle Scholar
  102. 102.
    Laklai H, Laval S, Dumartin L et al (2009) Thrombospondin-1 is a critical effector of oncosuppressive activity of sst2 somatostatin receptor on pancreatic cancer. Proc Natl Acad Sci U S A 106:17769–17774PubMedCrossRefGoogle Scholar
  103. 103.
    Hasskarl J, Kaufmann M, Schmid HA (2011) Somatostatin receptors in non-­neuroendocrine malignancies: the potential role of somatostatin analogs in solid tumors. Future Oncol 7:895–913PubMedCrossRefGoogle Scholar
  104. 104.
    Zhou T, Xiao X, Xu B et al (2009) Overexpression of SSTR2 inhibited the growth of SSTR2-­positive tumors via multiple signaling pathways. Acta Oncol 48:401–410PubMedCrossRefGoogle Scholar
  105. 105.
    Faivre S, Sablin MP, Dreyer C et al (2010) Novel anticancer agents in clinical trials for well-­differentiated neuroendocrine tumors. Endocrinol Metab Clin North Am 39:811–826PubMedCrossRefGoogle Scholar
  106. 106.
    Valentino J, Evers BM (2011) Recent advances in the diagnosis and treatment of gastrointestinal carcinoids. Adv Surg 45:285–300PubMedCrossRefGoogle Scholar
  107. 107.
    Florio T (2008) Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors. Front Biosci 13:822–840PubMedCrossRefGoogle Scholar
  108. 108.
    Jia WD, Xu GL, Wang W et al (2009) A somatostatin analogue, octreotide, inhibits the occurrence of second primary tumors and lung metastasis after resection of hepatocellular carcinoma in mice. Tohoku J Exp Med 218:155–160PubMedCrossRefGoogle Scholar
  109. 109.
    Zhao B, Yang P, Yang J et al (2011) A randomized trial of somatostatin to regulate the VEGFs/VEGFRs in patients with gastric cancer. Hepatogastroenterology 58:1425–1430PubMedCrossRefGoogle Scholar
  110. 110.
    Sun LC, Luo J, Mackey LV et al (2007) A conjugate of camptothecin and a somatostatin analog against prostate cancer cell invasion via a possible signaling pathway involving PI3K/Akt, alphaVbeta3/alphaVbeta5 and MMP-2/-9. Cancer Lett 246:157–166PubMedCrossRefGoogle Scholar
  111. 111.
    Kumar M, Liu ZR, Thapa L et al (2004) Anti-angiogenic effects of somatostatin receptor subtype 2 on human pancreatic cancer xenografts. Carcinogenesis 25:2075–2081PubMedCrossRefGoogle Scholar
  112. 112.
    Hall GH, Turnbull LW, Bedford K et al (2005) Neuropilin-1 and VEGF correlate with somatostatin expression and microvessel density in ovarian tumours. Int J Oncol 27:1283–1288PubMedGoogle Scholar
  113. 113.
    Carrere N, Vernejoul F, Souque A et al (2005) Characterization of the bystander effect of somatostatin receptor sst2 after in vivo gene transfer into human pancreatic cancer cells. Hum Gene Ther 16:1175–1193PubMedCrossRefGoogle Scholar
  114. 114.
    Molina-Infante J, Perez-Gallardo B (2011) Somatostatin analogues for bleeding gastrointestinal angiodysplasias: when should thalidomide be prescribed? Dig Dis Sci 56:266–267PubMedCrossRefGoogle Scholar
  115. 115.
    Fasciani A, Quilici P, Biscaldi E et al (2010) Overexpression and functional relevance of somatostatin receptor-1, -2, and -5 in endometrium and endometriotic lesions. J Clin Endocrinol Metab 95:5315–5319PubMedCrossRefGoogle Scholar
  116. 116.
    Prokosch V, Fink J, Heiduschka P et al (2011) VEGF, Ang-2 and SRIF associated abnormal postnatal development of the retinal capillary network in the Royal College of Surgeons rat. Exp Eye Res 92:128–137PubMedCrossRefGoogle Scholar
  117. 117.
    Simo R, Carrasco E, Garcia-Ramirez M et al (2006) Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr Diabetes Rev 2:71–98PubMedCrossRefGoogle Scholar
  118. 118.
    Palii SS, Afzal A, Shaw LC et al (2008) Nonpeptide somatostatin receptor agonists specifically target ocular neovascularization via the somatostatin type 2 receptor. Invest Ophthalmol Vis Sci 49:5094–5102PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Surgery, Division of Vascular and Endovascular SurgeryBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  2. 2.Department of SurgeryTufts Medical CenterBostonUSA

Personalised recommendations