Autophagy in fibroblasts induced by cigarette smoke extract promotes invasion in lung cancer cells
Journal
International Journal of Cancer
Date Issued
2020
Author(s)
Abstract
We investigated the effects of cigarette smoke extract (CSE) on lung fibroblasts and found that the invasiveness of lung cancer cells was facilitated by the conditioned medium from CSE-treated fibroblasts. CSE induced autophagy in fibroblasts and increased the expression of autophagy-related proteins, including optineurin and Ras-related protein Rab1B. Afterward, the fibroblasts produced high levels of interleukin-8 (IL-8), which promoted cancer cell invasion. The inhibition of either optineurin or Rab1B abrogated a rise in microtubule-associated protein 1 light chain 3 β and a decrease in p62 protein, as well as the production of IL-8, in CSE-treated fibroblasts. A three-dimensional invasion assay using cancer cell spheroids revealed that the invasion of cancer cells alone and the fibroblast-led cancer cell invasion were both enhanced by the conditioned media from CSE-treated fibroblasts. These results suggest that cigarette smoke may induce autophagy and IL-8 secretion in lung fibroblasts and modify the microenvironment to favor invasion of lung cancer cells. ? 2020 UICC
SDGs
Other Subjects
cigarette smoke; guanine nucleotide binding protein; interleukin 8; microtubule associated protein; microtubule associated protein 1 light chain 3beta; optineurin; Rab1B protein; sequestosome 1; unclassified drug; carrier protein; cell cycle protein; CXCL8 protein, human; interleukin 8; OPTN protein, human; Rab protein; Rab1B protein, human; Article; autophagy (cellular); controlled study; cytokine production; cytokine release; human; human cell; lung fibroblast; non small cell lung cancer; priority journal; protein expression; tumor invasion; tumor spheroid; adverse event; autophagy; cancer associated fibroblast; cell motion; conditioned medium; cytology; drug effect; gene knockdown; genetics; immunology; lung; lung tumor; metabolism; multicellular spheroid; non small cell lung cancer; pathology; smoke; smoking; tobacco; tumor cell line; tumor invasion; tumor microenvironment; Autophagy; Cancer-Associated Fibroblasts; Carcinoma, Non-Small-Cell Lung; Cell Cycle Proteins; Cell Line, Tumor; Cell Movement; Culture Media, Conditioned; Gene Knockdown Techniques; Humans; Interleukin-8; Lung; Lung Neoplasms; Membrane Transport Proteins; Neoplasm Invasiveness; rab1 GTP-Binding Proteins; Smoke; Smoking; Spheroids, Cellular; Tobacco; Tumor Microenvironment
Publisher
Wiley-Liss Inc.
Type
journal article