Laminin α1 orchestrates VEGFA functions in the ecosystem of colorectal carcinoma: Laminin α1 promotes colon tumourigenesis

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. Results: By 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. Conclusions: Together, we have identified VEGFA, CXCR4 and 21 integrin downstream of LM1 in colon cancer as of bad prognostic value for patient survival. Significance: This information opens novel opportunities for diagnosis and treatment of colon cancer.