Autophagy in fibroblasts induced by cigarette smoke extract promotes invasion in lung cancer cells

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. What's new? Autophagy in stromal cells may play an important role in cancer progression and therapy. Besides interactions between cancer cells and cancer‐associated fibroblasts, external stimulation could alter stromal autophagy in the tumor microenvironment. Here, the authors found that cigarette smoke extract induced autophagy in fibroblasts and increased the expression of autophagy‐related proteins. The fibroblasts produced high levels of IL‐8, which promoted cancer cell invasion. Using a 3D cellular spheroid culture, the authors also observed enhanced fibroblast‐led cancer cell invasion. Cigarette smoke may induce autophagy and IL‐8 secretion in lung fibroblasts and modify the microenvironment to favor invasion of lung cancer cells.