Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E
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Author(s)
Li, Hua-Jung
Herschman, Harvey R.
Reinhardt, Ferenc
Weinberg, Robert A
Date Issued
September 2012
Journal
Cancer Discovery
Publisher
American Association for Cancer Research (AACR)
Citation
Li, Hua-Jung, Ferenc Reinhardt, Harvey R. Herschman, and Robert A. Weinberg. “ Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E₂ Sgnaling.” Cancer Discovery 2, no. 9 (July 3, 2012): 840–855.
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Author's final manuscript
Abstract
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 (MSC), 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. SIGNIFICANCE: Although PGE₂ has been implicated time and again in fostering tumorigenesis, its effects on carcinoma cells that contribute specifically to tumor formation are poorly understood. Here we show that tumor cells are able to elicit a strong induction of the COX-2/microsomal prostaglandin-E synthase-1 (mPGES-1)/PGE₂ axis in MSCs recruited to the tumor-associated stroma by releasing IL-1, which in turn elicits a mesenchymal/stem cell–like phenotype in the carcinoma cells.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Division of Comparative Medicine
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DOI of Published Version
https://doi.org/10.1158/2159-8290.CD-12-0101
