Tumor Biology

, Volume 37, Issue 12, pp 15525–15534 | Cite as

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

Original Article
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Abstract

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.

Keywords

Nonsmall cell lung cancer (NSCLC) Myofibroblasts Transforming growth factor β 1 (TGFβ1) Vascular endothelial growth factor A (VEGF-A) 
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Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant 81401880), Funds from Shanghai government for talent development (Grant 201455), Medical-Engineering Joint Funds from Shanghai Jiao Tong University (Grant No. YG2013MS11), and Funds from Shanghai Chest Hospital [YZ13-15].

Conflict of interest

The authors have declared that no competing interests exist.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Shanghai Lung Tumor Clinical Medical CenterShanghai Chest Hospital Affiliated To Shanghai Jiaotong UniversityShanghaiChina

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