Abstract
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.
| Original language | English |
|---|---|
| Journal | Journal of Cellular Physiology |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2018 |
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Keywords
- Breast cancer
- EMT
- Fibroblasts
- Nicotine
- Tumor microenvironment
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Cell Biology
Cite this
Activation of fibroblasts by nicotine promotes the epithelial-mesenchymal transition and motility of breast cancer cells. / Chen, Pin Cyuan; Lee, Wen Ying; Ling, Hsiang Hsi; Cheng, Chia Hsiung; Chen, Ku Chung; Lin, Cheng Wei.
In: Journal of Cellular Physiology, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activation of fibroblasts by nicotine promotes the epithelial-mesenchymal transition and motility of breast cancer cells
AU - Chen, Pin Cyuan
AU - Lee, Wen Ying
AU - Ling, Hsiang Hsi
AU - Cheng, Chia Hsiung
AU - Chen, Ku Chung
AU - Lin, Cheng Wei
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - EMT
KW - Fibroblasts
KW - Nicotine
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85039796874&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039796874&partnerID=8YFLogxK
U2 - 10.1002/jcp.26334
DO - 10.1002/jcp.26334
M3 - Article
AN - SCOPUS:85039796874
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
ER -