Communication between human macrophages and epithelial cancer cell lines dictates lipid mediator biosynthesis.
Cell Mol Life Sci
; 77(21): 4365-4378, 2020 Nov.
Article
em En
| MEDLINE
| ID: mdl-31894359
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 levels. In contrast to cancer cells, coincubation with non-transformed human umbilical vein endothelial cells (HUVEC) did not affect LM production in MDM. Vice versa, MDM increased COX-2 protein expression and COX-mediated prostanoid formation in cancer cells. Conclusively, our data reveal that the communication between MDM and cancer cells can strikingly modulate the biosynthetic capacities to produce bioactive LM with potential relevance for tumor biology.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comunicação Celular
/
Células Epiteliais
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Metabolismo dos Lipídeos
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Neoplasias Pulmonares
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Macrófagos
Limite:
Humans
Idioma:
En
Revista:
Cell Mol Life Sci
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha