title: Soluble melanoma cell adhesion molecule (sMCAM/sCD146) promotes angiogenic effects on endothelial progenitor cells through angiomotin.
abstract: The melanoma cell adhesion molecule (CD146) contains a circulating proteolytic variant (sCD146), which is involved in inflammation and angiogenesis. Its circulating level is modulated in different pathologies, but its intracellular transduction pathways are still largely unknown. Using peptide pulldown and mass spectrometry, we identified angiomotin as a sCD146-associated protein in endothelial progenitor cells (EPC). Interaction between angiomotin and sCD146 was confirmed by enzyme-linked immunosorbent assay (ELISA), homogeneous time-resolved fluorescence, and binding of sCD146 on both immobilized recombinant angiomotin and angiomotin-transfected cells. Silencing angiomotin in EPC inhibited sCD146 angiogenic effects, i.e. EPC migration, proliferation, and capacity to form capillary-like structures in Matrigel. In addition, sCD146 effects were inhibited by the angiomotin inhibitor angiostatin and competition with recombinant angiomotin. Finally, binding of sCD146 on angiomotin triggered the activation of several transduction pathways that were identified by antibody array. These results delineate a novel signaling pathway where sCD146 binds to angiomotin to stimulate a proangiogenic response. This result is important to find novel target cells of sCD146 and for the development of therapeutic strategies based on EPC in the treatment of ischemic diseases.
authors: Inserm UMR-S 1076, Physiopathology of Endothelium, Aix-Marseille University, Formation and Research Unit of Pharmacy, 13005 Marseille, France.
authors: Jimmy
authors: J
authors: Stalin
authors: Karim
authors: K
authors: Harhouri
authors: Lucas
authors: L
authors: Hubert
authors: Caroline
authors: C
authors: Subrini
authors: Daniel
authors: D
authors: Lafitte
authors: Jean-Claude
authors: JC
authors: Lissitzky
authors: Nadia
authors: N
authors: Elganfoud
authors: Stéphane
authors: S
authors: Robert
authors: Alexandrine
authors: A
authors: Foucault-Bertaud
authors: Elise
authors: E
authors: Kaspi
authors: Florence
authors: F
authors: Sabatier
authors: Michel
authors: M
authors: Aurrand-Lions
authors: Nathalie
authors: N
authors: Bardin
authors: Lars
authors: L
authors: Holmgren
authors: Françoise
authors: F
authors: Dignat-George
authors: Marcel
authors: M
authors: Blot-Chabaud
mesh_terms: D000091082:Angiomotins; D043168:Angiostatins / Q000378:metabolism; D051929:CD146 Antigen / Q000097:blood*; D002196:Capillaries / Q000378:metabolism; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D020868:Gene Silencing; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins; D008856:Microscopy, Fluorescence / Q000379:methods; D009389:Neovascularization, Pathologic; D011509:Proteoglycans / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence / Q000379:methods; D013234:Stem Cells / Q000166:cytology*; D014945:Wound Healing
chemical_list: C423985:AMOT protein, human; D000091082:Angiomotins; D051929:CD146 Antigen; D004338:Drug Combinations; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011509:Proteoglycans; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C059485:matrigel; D043168:Angiostatins; D003094:Collagen
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