Cancer-stimulated mesenchymal stem cells create a carcinoma stem-cell niche via Prostaglandin E2 signaling
Menée in vitro et in vivo, cette étude met en évidence un mécanisme par lequel des cellules souches du mésenchyme, via la production de prostaglandine E2 et de diverses cytokines, induisent la formation d'une niche de cellules souches cancéreuses
Mesenchymal cells of the tumor-associated stroma are critical determinants of carcinoma cell behavior. We focus here on interactions of carcinoma cells with mesenchymal stem cells (MSCs), which are recruited to the tumor stroma and, once present, are able to influence the phenotype of the carcinoma cells. We find that carcinoma cell-derived interleukin-1 (IL-1) induces prostaglandin E2 (PGE2) secretion by MSCs. The resulting PGE2 operates in an autocrine manner, cooperating with ongoing paracrine IL-1 signaling, to induce expression of a group of cytokines by the MSCs. The PGE2 and cytokines then proceed to act in a paracrine fashion on the carcinoma cells to induce activation of β-catenin signaling and formation of cancer stem cells. These observations indicate that MSCs and derived cell types create a cancer stem-cell niche to enable tumor progression via release of PGE2 and cytokines.
Cancer Discovery 2012