TY - JOUR T1 - Laminin α1 orchestrates VEGFA functions in the ecosystem of colorectal carcinoma JF - bioRxiv DO - 10.1101/099465 SP - 099465 AU - E. Mammadova-Bach AU - T. Rupp AU - C. Spenlé AU - I. Jivkov AU - P. Shankaranarayanan AU - A. Klein AU - L. Pisarsky AU - A. Méchine-Neuville AU - G. Cremel AU - M. Kedinger AU - O. De Wever AU - N. Ambartsumian AU - S. Robine AU - E. Pencreach AU - D. Guenot AU - J.G. Goetz AU - P. Simon-Assmann AU - G. Orend AU - O. Lefebvre Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/01/10/099465.abstract N2 - 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 tumorstroma 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.BMbasement membraneECMextracellular matrixLMlamininvLMα1villin-LMα1 transgenic miceCAFscancer-associated fibroblastsIFimmunofluorescenceVEGFvascular endothelial growth factor. ER -