Cigarette smoke induces cell motility via platelet‐activating factor accumulation in breast cancer cells: a potential mechanism for metastatic disease. Issue 3 (22nd March 2015)

• Record Type: Journal Article
• Authors: Kispert, Shannon; Marentette, John; McHowat, Jane
• Is Part Of: Physiological reports. Volume 3:Issue 3(2015:Mar.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2015-03-22
• Subjects: Breast cancer -- cigarette smoke -- motility -- platelet‐activating factor; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.12318
• Languages: English
• ISSNs: 2051-817X

Abstract

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 detail. We propose that cigarette smoking contributes to metastatic disease via inhibition of breast cancer cell platelet‐activating factor acetylhydrolase (PAF‐AH), resulting in PAF accumulation and a subsequent increase in cell motility. We studied several breast cell lines, including immortalized mammary epithelial cells (MCF‐10A), luminal A hormone positive MCF‐7, basal‐like triple negative MDA‐MB‐468, and claudin‐low triple‐negative highly metastatic MDA‐MB‐231 breast tumor cells. We exposed cells to cigarette smoke extract (CSE) for up to 48 h. CSE inhibited PAF‐AH activity, increased PAF accumulation, and increased cell motility in MDA‐MB‐231 metastatic triple negative breast cancer cells. The calcium‐independent phospholipase A2 (iPLA2 ) inhibitor, ( S ) bromoenol lactone (( S ) ‐ BEL) was used to prevent the accumulation of PAF and further prevented the increase in cell motility seen previously when cells were exposed to CSE. Thus, iPLA2 or PAF may represent a therapeutic target to manage metastatic disease, particularly in triple‐negative breast cancer patients who smoke. Abstract : Exposure of human breast cancer cells to cigarette smoke extract resulted in PAF accumulation and increased cell motility. These responses were blocked by pretreating cells with a calcium‐independent phospholipase A2 inhibitor.