Alexandria Tobin - October 28, 2019

The role of lipoprotein lipase in the growth and progression of breast cancer

Lipoprotein lipase (LPL) is an extracellular lipase that hydrolyzes triglycerides and phospholipids from circulating lipoproteins, promoting the delivery of hydrolyzed lipids to cells. LPL is highly expressed in the adipose tissue surrounding breast tumors. The hydrolysis products generated by LPL are used by cells as components of the cell membrane, as an energy supply, and as signalling molecules. Therefore, the presence of LPL on or around cancer cells may contribute to the growth and progression of breast cancer tumors. Thus, we hypothesize that the hydrolysis products generated by LPL from lipoproteins can promote increased cell viability and pro-inflammatory cytokine secretion from breast cancer cells. Pro-inflammatory cytokines create a favourable microenvironment that promotes breast cancer progression and metastasis. In the presence of lipoprotein hydrolysis products generated by LPL from total lipoproteins, the metabolic activity of MCF-7, T47D, MDA-MB-231, and SKBR3 breast cancer cell lines is significantly higher than controls. Ongoing work is focused on analyzing the effect of total lipoprotein hydrolysis products on the cytokine secretion profile of various breast cancer cell lines. To date, using cytokine arrays, a significant increase in the secretion of some cytokines and chemokines (IL-6, IL-8, IL-4, TNF-α, CXCL1, CXCL11, CCL5, ICAM-1) of 2- to 10-fold was observed in cells treated with lipoprotein hydrolysis products compared to control. In contrast, MCF-7 cells showed a decrease in the secretion of fewer cytokines (IL-1α, IL-27). The results of this study will provide information on how LPL within the tumor microenvironment affects breast cancer cell viability and can influence the progression of breast cancer.

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