Induction of lung epithelial cell transformation and fibroblast activation by Yunnan tin mine dust and their interaction.
Tumor-stroma interactions play a significant role in tumor development and progression. Our study employed an in vitro co-culture model of epithelial cells and fibroblasts to investigate the mechanism of and interaction between lung epithelial cell transformation and fibroblast activation induced by Yunnan tin mine dust. Epithelial cell transformation was evaluated using concanavalin A agglutination and anchorage-independent growth assays, and fibroblast activation was assessed via immunohistochemistry. The TGF-β1/Smad pathway was monitored by Western blot analysis and ELISA. We found concanavalin A agglutination and anchorage-independent growth assays of dust-exposed epithelial cells were positive, dust-exposed fibroblasts expressed α-SMA, and during the mine dust-induced tumorigenesis, TGF-β1/Smad signaling pathway changed. In conclusion, Yunnan tin mine dust is able to induce the malignant transformation of bronchial epithelial cells and fibroblast activation. Epithelial cells are the main target of mine dust. Bronchial epithelial cell transformation and fibroblast activation are correlated and synergistic. Their interdependence is related to the TGF-β1/Smad signaling pathway.
Bian
Li
L
Department of Pathology, The First Affiliated Hospital of Kunming Medical College, 650032 Kunming, China.
He
Yong-Wen
YW
Tang
Rui-Zhu
RZ
Ma
Li-Ju
LJ
Wang
Chun-Yan
CY
Ruan
Yong-Hua
YH
Gao
Qian
Q
Jin
Ke-Wei
KW
D000199:Actins / Q000378:metabolism; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002681:China; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004391:Dust; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008906:Mining; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D014001:Tin / Q000633:toxicity*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
C541116:ACTA2 protein, human; D000199:Actins; D004391:Dust; D051785:Smad Proteins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014001:Tin