Lipoprotein Lipase Hydrolysis Products Induce Pro-Inflammatory Cytokine Expression in Triple-Negative Breast Cancer Cells

Abstract Objectives: Lipoprotein lipase (LPL) is an extracellular lipase that hydrolyzes triacylglycerols and phospholipids from lipoproteins. LPL is highly expressed in adipose tissue and expressed in some breast cancer cell lines. Hydrolysis products generated by LPL can be used by cells as components of the cell membrane, as an energy supply, or as signaling molecules. Therefore, LPL on or around cancer cells may contribute to breast cancer growth and progression. We hypothesized that hydrolysis products generated by LPL from total lipoproteins can promote pro-inflammatory cytokine secretion from breast cancer cells and/or affect viability. Results: Using cytokine arrays, we found that the secretion of seven cytokines was increased by MDA-MB-231 cells treated with lipoprotein hydrolysis products. An increased secretion of TNF-α and IL-6 was also seen by MDA-MB-468 cells, and an increase in IL-4 secretion was seen by MDA-MB-468 and SKBR3 cells. In contrast, MCF-7 cells showed a decreased secretion of only two cytokines. The changes to cytokine secretion profiles by the breast cancer cell types, including by non-cancerous MCF-10a breast cells, were independent of increased cell metabolic activity. Overall, these results provide information on how lipoprotein hydrolysis products within the tumor microenvironment might affect breast cancer cell viability and tumor progression.