Laminin 1 Orchestrates Vegfa Functions In The Ecosystem Of Colorectal Carcinoma

Background InformationTumor 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.ResultsBy employing mouse models expressing high and low levels of the laminin 1 chain (LM1), 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 LM1, VEGFA expression triggered by the complex integrin 21-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.ConclusionsTogether, we have identified VEGFA, CXCR4 and 21 integrin downstream of LM1 in colon cancer as of bad prognostic value for patient survival.SignificanceThis information opens novel opportunities for diagnosis and treatment of colon cancer.