Different roles of myofibroblasts in the tumorigenesis of nonsmall cell lung cancer

Myofibroblasts play a critical role in the cancer cell growth, invasion, and tumor-associated vascularization during the carcinogenesis of nonsmall cell lung cancer (NSCLC), whereas the underlying molecular bases are not completely understood. We isolated Lin-negative, Sca1-low, and CD49c-high myofibroblasts from the NSCLC tissues of the patients and modified the levels of either transforming growth factor beta 1 (TGF beta 1) or vascular endothelial growth factor A (VEGF-A) in these cells. We found that coculture with TGF beta 1-overexpressing myofibroblasts significantly decreased the NSCLC cell growth in an MTT assay through proliferation suppression rather than modulation of cell apoptosis, while significantly increased the NSCLC cell invasiveness in either a transwell migration assay or a scratch wound healing migration assay. However, modulation of TGF beta 1 levels in myofibroblasts did not significantly alter vessel formation in a human umbilical vein endothelial cells (HUVECs) transwell collagen gel assay. On the other hand, overexpression of VEGF-A in myofibroblasts significantly increased vessel formation in the HUVECs transwell collagen gel assay. Together, these data suggest that myofibroblasts may regulate cancer cell growth and invasion through TGF beta 1 but modulate cancer-associated neovascularization through VEGF-A. Hence, targeting different signaling pathways in myofibroblasts may delicately control NSCLC growth and invasion.