Cigarette smoke increases PAF accumulation, cell motility and EMT in triple negative breast cancer cells (58.8)

Abstract

Most cancer deaths are a result of metastasis rather than the primary tumor. Although cigarette smoking has been determined as a risk factor for several cancers, its role in metastasis has not been studied in great detail. We propose that cigarette smoking plays a role in increased metastasis via inhibition of endothelial cell platelet‐activating factor acetylhydrolase (PAF‐AH) inhibition, resulting in PAF accumulation and recruitment of circulating tumor cells to secondary sites. We exposed mammary epithelial cells (MCF‐10A) and breast cancer cell lines (MCF‐7, MDA‐MB‐231, and MDA‐MB‐468) to CSE for up to 48 hours. CSE inhibited PAF‐AH activity, increased PAF accumulation, and increased cell motility in the metastatic triple negative breast cancer cell line MDA‐MB‐231. Metastatic triple negative breast cancer cells exposed to CSE showed an increase in epithelial‐mesenchymal transition (EMT) as measured by the disappearance of the epithelial marker E‐cadherin and increased expression of the mesenchymal markers Snail and Slug. Thus, PAF may be a therapeutic target to manage metastatic disease, particularly in triple negative breast cancer patients who smoke.