ELUCIDATE THE MECHANISM OF PLATELET ACTIVATING FACTOR INDUCED TRANSFORMATION IN BREAST EPITHELIAL CELLS

Abstract

Microenvironment and tumour infiltrates play a crucial role in the different stages of development of cancer. Studies revealed that breast cancer cells upon stimulation with growth factors secrete phospholipid mediators such as lysophosphatidic acid, prostaglandins and platelet activating factor (PAF). PAF has been shown to play a role in platelet aggregation, inflammatory response, stimulation of neutrophil and macrophages, in allergic response and also in cancer development such as ovarian cancer, esophageal squamous cell carcinoma and breast cancer. It was also shown that cigarette smoke can inhibit platelet-activating factor acetylhydrolase in breast cancer cells and result in increased motility due to accumulation of PAF. Recent studies in lab demonstrated that PAF has the ability to enhance the migratory potential of breast cancer cells through JNK and/or PI3K pathway apart from this,it was also demonstrated that PAF treatment on MCF10A- an immortalized non tumorigenic near normal breast epithelial cell grown as 3D ‘on top’ cultures lead to morphological changes such as partially filled lumen, increased acinar volume and formation of protrusions; suggesting a potential role of PAF in transformation. The present study investigated the role of PAF induced transformation in the breast epithelial cells and its underlying mechanism. The result showed that PAF treatment on 3D ‘on top’ cultures leads to apical and basal polarity disruption and diffused cell-cell junction resembling epithelial to mesenchymal transition further confirmed using western blotting for EMT markers.Studies also confirmed over production and secretion of matrix metalloproteinases (MMP) such as MMP9 and MMP2 upon PAF treatment and also enhanced cell proliferation.