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

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.

NNK from tobacco smoking enhances pancreatic cancer cell stemness and chemoresistance by creating a β2AR‐Akt feedback loop that activates autophagy

“…Hence, we applied another autophagy inhibitor, autophinib, and got a similar result as CQ treatment. Therefore, studies on autophagy disorders caused by tobacco metabolites can be confirmed, and this phenomenon also exists in other tumors [43,44].…”

The interplay between oxidative stress and autophagy: focus on the development of neurological diseases

“…Inhibition optineurin reversed the pathway and reduced p62 protein and IL-8 expression in these treated fibroblasts. Thus, it seems that the IL‐8 expression of cigarette smoke triggered autophagy can support the spread of cancerous lung cells [ 128 ].…”

The role of cancer stromal fibroblasts in mediating the effects of tobacco-induced cancer cell growth

“…Besides, cancer cells can promote autophagy in fibroblasts and induce the release of inflammatory cytokines such as IL6 and IL8 which in turn promote the growth of tumor [ 36 ]. Among previous studies, we have observed tobacco induced autophagy in different kinds of fibroblasts like CAFs of breast cancer [ 37 ] and human lung fibroblasts [ 38 ]. Hou et al verified that exposed to cigarette smoke extract can up-regulate the expression of autophagy-related protein (LB3 and p62) in fibroblasts and promote the secretion of IL8 [ 38 ].…”

“…Among previous studies, we have observed tobacco induced autophagy in different kinds of fibroblasts like CAFs of breast cancer [ 37 ] and human lung fibroblasts [ 38 ]. Hou et al verified that exposed to cigarette smoke extract can up-regulate the expression of autophagy-related protein (LB3 and p62) in fibroblasts and promote the secretion of IL8 [ 38 ]. It seems that autophagy in stromal fibroblasts caused by external stimuli could also affect the development of cancer cells.…”