Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E
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 c...
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| Format: | Article |
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American Association for Cancer Research (AACR)
2018
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| Online Access: | http://hdl.handle.net/1721.1/116971 https://orcid.org/0000-0002-0895-3557 |
| _version_ | 1811092700144861184 |
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| author | Li, Hua-Jung Herschman, Harvey R. Reinhardt, Ferenc Weinberg, Robert A |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Li, Hua-Jung Herschman, Harvey R. Reinhardt, Ferenc Weinberg, Robert A |
| author_sort | Li, Hua-Jung |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:22:34Z |
| format | Article |
| id | mit-1721.1/116971 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:22:34Z |
| publishDate | 2018 |
| publisher | American Association for Cancer Research (AACR) |
| record_format | dspace |
| spelling | mit-1721.1/1169712022-10-02T02:31:23Z Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E Li, Hua-Jung Herschman, Harvey R. Reinhardt, Ferenc Weinberg, Robert A Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Division of Comparative Medicine Reinhardt, Ferenc Weinberg, Robert A 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. Breast Cancer Research Foundation National Institutes of Health (U.S.) (U54CA163109) Massachusetts Institute of Technology. Ludwig Center for Cancer Research 2018-07-13T13:45:12Z 2018-07-13T13:45:12Z 2012-09 2018-07-12T17:32:29Z Article http://purl.org/eprint/type/JournalArticle 2159-8274 2159-8290 http://hdl.handle.net/1721.1/116971 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. https://orcid.org/0000-0002-0895-3557 http://dx.doi.org/10.1158/2159-8290.CD-12-0101 Cancer Discovery Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research (AACR) PMC |
| spellingShingle | Li, Hua-Jung Herschman, Harvey R. Reinhardt, Ferenc Weinberg, Robert A Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E |
| title | Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E |
| title_full | Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E |
| title_fullStr | Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E |
| title_full_unstemmed | Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E |
| title_short | Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E |
| title_sort | cancer stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin e |
| url | http://hdl.handle.net/1721.1/116971 https://orcid.org/0000-0002-0895-3557 |
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