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 CD49e-high myofibroblasts from the NSCLC tissues of the patients and modified the levels of either transforming growth factor β 1 (TGFβ1) or vascular endothelial growth factor A (VEGF-A) in these cells. We found that coculture with TGFβ1-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 TGFβ1 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 TGFβ1 but modulate cancer-associated neovascularization through VEGF-A. Hence, targeting different signaling pathways in myofibroblasts may delicately control NSCLC growth and invasion.
Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital Affiliated To Shanghai Jiaotong University, 241 Huaihai West Road, Shanghai, 200030, China.
Jia
J
Huang
Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital Affiliated To Shanghai Jiaotong University, 241 Huaihai West Road, Shanghai, 200030, China.
Ziming
Z
Li
Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital Affiliated To Shanghai Jiaotong University, 241 Huaihai West Road, Shanghai, 200030, China.
Zhengping
Z
Ding
Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital Affiliated To Shanghai Jiaotong University, 241 Huaihai West Road, Shanghai, 200030, China. wen_li14@163.com.
Qingquan
Q
Luo
Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital Affiliated To Shanghai Jiaotong University, 241 Huaihai West Road, Shanghai, 200030, China. shun_lu14@163.com.
Shun
S
Lu
Myofibroblasts; Nonsmall cell lung cancer (NSCLC); Transforming growth factor β 1 (TGFβ1); Vascular endothelial growth factor A (VEGF-A)