ITGA11 expression of CAF promotes tumorigenicity and metastasis in NSCLC
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ABSTRACT: 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.
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE51722 | GEO | 2015/07/15
SECONDARY ACCESSION(S): PRJNA229136
REPOSITORIES: GEO
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