Proadrenomedullin NH2-terminal 20 peptide is a potent angiogenic factor, and its inhibition results in reduction of tumor growth

Cancer Research
A MartínezF Cuttitta

Abstract

We have found through ex vivo and in vivo angiogenesis models that the adrenomedullin gene-related peptide, proadrenomedullin NH2-terminal 20 peptide (PAMP), exhibits a potent angiogenic potential at femtomolar concentrations, whereas classic angiogenic factors such as vascular endothelial growth factor and adrenomedullin mediate a comparable effect at nanomolar concentrations. We found that human microvascular endothelial cells express PAMP receptors and respond to exogenous addition of PAMP by increasing migration and cord formation. Exposure of endothelial cells to PAMP increases gene expression of other angiogenic factors such as adrenomedullin, vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived growth factor C. In addition, the peptide fragment PAMP(12-20) inhibits tumor cell-induced angiogenesis in vivo and reduces tumor growth in xenograft models. Together, our data demonstrate PAMP to be an extremely potent angiogenic factor and implicate this peptide as an attractive molecular target for angiogenesis-based antitumor therapy.

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Citations

Feb 26, 2010·Cell and Tissue Research·Eva Vergaño-VeraAlfredo Martínez
Jun 2, 2005·Cancer Letters·Alfredo Martínez
Dec 6, 2005·Nature Reviews. Cancer·Alfredo MartínezMiguel Freire
Nov 1, 2006·Prostate Cancer and Prostatic Diseases·E C NelsonC P Evans
Apr 16, 2005·Neuro-oncology·Balveen KaurErwin G Van Meir
Sep 18, 2010·Expert Opinion on Therapeutic Targets·Jean-Laurent DevilleLaurent Daniel
Dec 6, 2014·Journal of Translational Medicine·Ignacio M LarráyozAlfredo Martínez
Feb 1, 2011·International Journal of Cancer. Journal International Du Cancer·Claudio NapoliFilomena De Nigris
Oct 22, 2013·Progress in Biophysics and Molecular Biology·Rajesh N Gacche, Rohan J Meshram
Oct 28, 2005·British Journal of Cancer·L L NikitenkoR Bicknell
Mar 31, 2018·Molecular Neurobiology·Hilda FerreroMaría J Ramírez
Jun 2, 2007·Pharmacological Reviews·Domenico RibattiGastone G Nussdorfer
Dec 6, 2019·Journal of Cellular Biochemistry·James L MulshineJohn D Minna
Feb 16, 2012·Endocrinology·Ignacio M Larráyoz, Alfredo Martínez
Mar 2, 2013·The Journal of Clinical Endocrinology and Metabolism·Sonia Martínez-Herrero, Alfredo Martínez
Feb 14, 2014·Molecular Cancer Research : MCR·Johnny A SenaCheng-Jun Hu

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