Communication between human macrophages and epithelial cancer cell lines dictates lipid mediator biosynthesis.

Communication between human macrophages and epithelial cancer cell lines dictates lipid mediator biosynthesis. Cell Mol Life Sci. 2020 Jan 01;: Authors: Werner M, Pace S, Czapka A, Jordan PM, Gerstmeier J, Koeberle A, Werz O Abstract In tumors, cancer cells coexist and communicate with macrophages that can promote tumorigenesis via pro-inflammatory signals. Lipid mediators (LMs), produced mainly by cyclooxygenases (COXs) or lipoxygenases (LOs), display a variety of biological functions with advantageous or deleterious consequences for tumors. Here, we investigated how the communication between human monocyte-derived M2-like macrophages (MDM) and cancer cells affects LM biosynthesis using LM metabololipidomics. Coculture of human MDM with human A549 epithelial lung carcinoma cells, separated by a semipermeable membrane, increased LM formation by MDM upon subsequent activation. Strongest effects were observed on 5-LO-derived LM. While expression of the 5-LO pathway was not altered, p38 MAPK and the downstream MAPKAPK-2 that phosphorylates and stimulates 5-LO were more susceptible for activation in MDM upon precedent coculture with A549 cells as compared to monocultures. Accordingly, the p38 MAPK inhibitor Skepinone-L selectively prevented this increase in 5-LO product formation. Also, 5-LO-/15-LO-derived LM including lipoxin A4, resolvin D2 and D5 were elevated after coculture with A549 cells, correlating to increased 15-LO-1 protein l...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research