ITGA11 expression of CAF promotes tumorigenicity and metastasis in NSCLC

Integrin alpha-11-beta-1 is stroma specific receptor for fibrillar collagen, as it is mainly over-expressed in carcinoma-associated fibroblasts (CAFs). However, its direct role in cancer progression remains unclear. We have investigated this role by generating severe combined immune deficient (SCID) mice deficient in integrin alpha-11 (alpha-11) expression. The growth of A549 lung adenocarcinoma cells in integrin alpha-11 knockout animals (alpha-11-/-) was significantly impeded, as compared to wild type (alpha-11+/+) SCID mice. Orthotopic implantation of a spontaneously metastatic NCI-H460SM cells into the lungs of alpha-11-/- and alpha-11+/+ mice showed significant reduction in the metastatic potential of these cells in the alpha-11 deficient mice. Our data support an important role for alpha-11 signaling pathway in CAFs, promoting tumor growth and metastatic potential of non-small cell lung cancer (NSCLC) cells by regulating the expression of alpha-SMA and stromal collagen-cross linking genes as the latter affects the organization and stiffness of fibrillar collagen. Lung cancer cell line A549 was subcutaneously implanted into integrin alpha 11 +/+, +/-, and -/- SCID mice. Each group had 8 mice. RNA from tumors from the 8 mice was pooled and splited into 2, one for human chip for the profiling gene expression of the tumor and the other for mouse chip for the profiling of stromal gene expression. 2 replicates for each group.