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

Autor: Pin Cyuan Chen, Hsiang Hsi Ling, Cheng Wei Lin, Wen Ying Lee, Chia Hsiung Cheng, Ku Chung Chen
Rok vydání: 2018
Předmět:
0301 basic medicine
Nicotine
Epithelial-Mesenchymal Transition
alpha7 Nicotinic Acetylcholine Receptor
Physiology
Clinical Biochemistry
Breast Neoplasms
Tumor initiation
03 medical and health sciences
0302 clinical medicine
Cancer-Associated Fibroblasts
Cell Movement
Transforming Growth Factor beta
Paracrine Communication
Tumor Microenvironment
medicine
Humans
Neoplasm Invasiveness
Epithelial–mesenchymal transition
Tumor microenvironment
biology
Chemistry
Smoking
Connective Tissue Growth Factor
Intracellular Signaling Peptides and Proteins
Cell Biology
Transforming growth factor beta
CTGF
030104 developmental biology
Culture Media
Conditioned
Transcriptional Coactivator with PDZ-Binding Motif Proteins
030220 oncology & carcinogenesis
Carcinogens
MCF-7 Cells
Trans-Activators
biology.protein
Cancer research
Female
Proto-Oncogene Proteins c-akt
Signal Transduction
Transcription Factors
medicine.drug
Transforming growth factor
Zdroj: Journal of Cellular Physiology. 233:4972-4980
ISSN: 0021-9541
DOI: 10.1002/jcp.26334
Popis: 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)-β by nicotine-treated fibroblasts was demonstrated to be crucial for promoting the EMT and cancer cell migration, and blocking of CTGF and TGF-β in Nic-CM-suppressed tumor motility. Moreover, nicotine induced expressions of CTGF, and TGF-β in fibroblasts as identified through α7 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.
Databáze: OpenAIRE
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