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Targeting soluble CD146 with a neutralizing antibody inhibits vascularization, growth and survival of CD146-positive tumors

M Stalin 1, 2 M Nollet 1, 2 Philippe Garrigue 1, 2 Suzanne Fernandez 3 M Vivancos 1, 2 M Essaadi 1, 2 M Muller 1, 2 M Bachelier 1, 2 Alexandrine Foucault-Bertaud 1, 2 F Fugazza 4 Aurelie S Leroyer 1, 2 Nathalie Bardin 1, 2 M Guillet 1, 2 Francoise Dignat-George 5, 1, 2 M Blot-Chabaud 1, 2
1 VRCM - Vascular research center of Marseille
2 Physiopathologie de l'Endothelium
VRCM - Vascular research center of Marseille
3 CERIMED - Centre Européen de Recherche en Imagerie médicale
4 ADV ACCELERATOR APPLICAT, COLLERETTO GIACOSA,, TO ITALY
5 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
Abstract : CD146 (MUC-18, MCAM) expression on cancer cells correlates with cancer progression and a bad prognosis in several tumors, including melanoma and pancreatic tumors. Deciphering the mechanism mediating the CD146 role in cancer is essential for generating new therapeutic strategies. We found that CD146 expression in cancer cells is associated with a secretion of soluble CD146 (sCD146) that constitutes an active player in tumor development. Indeed, sCD146 induces the overexpression of its binding protein, angiomotin, on both endothelial and cancer cells and promotes both paracrine effects on angiogenesis and autocrine effects on cancer cells proliferation and survival. These last effects are mediated in part through the induction and phosphorylation of c-myc in cancer cells. In mice models xenografted with human CD146-positive melanoma or pancreatic cancer cells, administration of a novel monoclonal antibody specifically targeting sCD146, but not its membrane form, successfully suppresses tumor vascularization and growth. Our findings demonstrate that sCD146 secreted by CD146-positive tumors mediates important pro-angiogenic and pro-tumoral effects. Targeting sCD146 with a novel neutralizing antibody could thus constitute an innovative therapeutic strategy for the treatment of CD146-positive tumors.
Keywords : THERAPY PROSTATE-CANCER C-MYC EXPRESSION ENDOTHELIAL PROGENITOR CELLS HUMAN BREAST-CANCER HUMAN-MELANOMA ADHESION MOLECULE ANGIOGENESIS ANGIOMOTIN
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https://hal-amu.archives-ouvertes.fr/hal-01456904
Contributor : Françoise Dignat-George Connect in order to contact the contributor
Submitted on : Monday, February 6, 2017 - 9:49:49 AM
Last modification on : Wednesday, January 19, 2022 - 2:04:02 PM

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  • HAL Id : hal-01456904, version 1
  • PUBMED : 27065325

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UNIV-AMU | CNRS | EC-MARSEILLE

Citation

M Stalin, M Nollet, Philippe Garrigue, Suzanne Fernandez, M Vivancos, et al.. Targeting soluble CD146 with a neutralizing antibody inhibits vascularization, growth and survival of CD146-positive tumors. Oncogene, Nature Publishing Group, 2016, 35, pp.5489-5500. ⟨hal-01456904⟩

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