Activation of fibroblasts by nicotine promotes the epithelial-mesenchymal transition and motility of breast cancer cells

作者：Chen Pin Cyuan; Lee Wen Ying; Ling Hsiang Hsi; Cheng Chia Hsiung; Chen Ku Chung; Lin Cheng Wei^*

来源：Journal of Cellular Physiology, 2018, 233(6): 4972-4980.

DOI：10.1002/jcp.26334

• breast cancer
• EMT
• fibroblasts
• nicotine
• tumor microenvironment

The tumor microenvironment plays an important role in tumor initiation and progression. It is well documented that nicotine participates in cigarette smoking-related malignancies. Previous studies focused on the effects of nicotine on tumor cells; however, the role of the microenvironment in nicotine-mediated tumorigenesis is poorly understood. Herein, we investigated the effect and molecular mechanism of nicotine on fibroblasts and its contribution to breast cancer. We found that nicotine induced the epithelial-mesenchymal transition (EMT) of breast cancer cells and promoted activation of fibroblasts. Interestingly, conditioned medium from nicotine-activated fibroblasts (Nic-CM) had a greater impact on promoting the EMT and migratory capability toward cancer cells than did treatment with nicotine alone. Production of connective tissue growth factor (CTGF) and transforming growth factor (TGF)- by nicotine-treated fibroblasts was demonstrated to be crucial for promoting the EMT and cancer cell migration, and blocking of CTGF and TGF- in Nic-CM-suppressed tumor motility. Moreover, nicotine induced expressions of CTGF, and TGF- in fibroblasts as identified through 7 nicotinic acetylcholine receptor (nAChR)-dependent activation of the AKT/TAZ signaling mechanism. Together, our data showed for the first time that activation of fibroblasts is largely responsible for accelerating smoking-mediated breast cancer progression.

• 出版日期2018-6
• 单位河北医科大学