| Affiliation: | 1. Graduate Institute of Oral Biology, College of Medicine, National Taiwan University, Taipei, Taiwan;2. Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan;3. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan;4. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan |
| 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. |
