Laminin α1 orchestrates VEGFA functions in the ecosystem of colorectal carcinoma.
Fiche publication
Date publication
juin 2018
Journal
Biology of the cell
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GOETZ Jacky, Dr GUENOT Dominique, Dr LEFEBVRE Olivier, Dr OREND Gertraud, Dr PENCREACH Erwan
Tous les auteurs :
Mammadova-Bach E, Rupp T, Spenlé C, Jivkov I, Shankaranarayanan P, Klein A, Pisarsky L, Méchine-Neuville A, Cremel G, Kedinger M, De Wever O, Ambartsumian N, Robine S, Pencreach E, Guenot D, Simon-Assmann P, Goetz JG, Orend G, Lefebvre O
Lien Pubmed
Résumé
Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumor-stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth. The underlying mechanism involves attraction of carcinoma-associated fibroblasts by LMα1, VEGFA expression triggered by the complex integrin α2β1-CXCR4 and binding of VEGFA to LM-111, which in turn promotes angiogenesis, tumor cell survival and proliferation. A gene signature comprising LAMA1, ITGB1, ITGA2, CXCR4 and VEGFA has negative predictive value in colon cancer. Together, this information opens novel opportunities for diagnosis and anti-cancer targeting. This article is protected by copyright. All rights reserved.
Mots clés
Laminin α1, cancer-associated cancer, colorectal cancer, tumour angiogenesis, vascular endothelial growth factor
Référence
Biol. Cell. 2018 Jun 15;: