Laminin α1 orchestrates VEGFA functions in the ecosystem of colorectal carcinoma.

BACKGROUND INFORMATION: 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.

RESULTS: 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.

CONCLUSIONS: Together, we have identified VEGFA, CXCR4 and α2β1 integrin downstream of LMα1 in colon cancer as of bad prognostic value for patient survival.

SIGNIFICANCE: This information opens novel opportunities for diagnosis and treatment of colon cancer.