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

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Tumor Biology

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.

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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].

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The authors have declared that no competing interests exist.

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    Authors and Affiliations

    1. Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital Affiliated To Shanghai Jiaotong University, 241 Huaihai West Road, Shanghai, 200030, China

      Jia Huang, Ziming Li, Zhengping Ding, Qingquan Luo & Shun Lu

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    1. Jia Huang
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    2. Ziming Li
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    3. Zhengping Ding
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    4. Qingquan Luo
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    Correspondence to Qingquan Luo or Shun Lu.

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    Jia Huang and Ziming Li contributed equally to this work.

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    Huang, J., Li, Z., Ding, Z. et al. Different roles of myofibroblasts in the tumorigenesis of nonsmall cell lung cancer. Tumor Biol. 37, 15525–15534 (2016). https://doi.org/10.1007/s13277-015-3862-8

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    • DOI: https://doi.org/10.1007/s13277-015-3862-8

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