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Autocrine Factors Produced by Mesenchymal Stem Cells in Response to Cell–Cell Contact Inhibition Have Anti-Tumor Properties
Recently, mesenchymal stem cell (MSC) therapies have been questioned as MSCs are capable of both promoting and inhibiting tumorigenesis. Both MSCs and tumor cells replicate to increase their population size; however, MSCs, but not tumor cells, stop dividing when they reach confluence due to cell–cel...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486504/ https://www.ncbi.nlm.nih.gov/pubmed/37681882 http://dx.doi.org/10.3390/cells12172150 |
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author | Chen, Jerry P. Li, Rong Jiang, Jean X. Chen, Xiao-Dong |
author_facet | Chen, Jerry P. Li, Rong Jiang, Jean X. Chen, Xiao-Dong |
author_sort | Chen, Jerry P. |
collection | PubMed |
description | Recently, mesenchymal stem cell (MSC) therapies have been questioned as MSCs are capable of both promoting and inhibiting tumorigenesis. Both MSCs and tumor cells replicate to increase their population size; however, MSCs, but not tumor cells, stop dividing when they reach confluence due to cell–cell contact inhibition and then differentiate. We hypothesized that contact inhibition results in the production of effector molecules by confluent MSCs and these effectors are capable of suppressing tumor cell growth. To test this hypothesis, we co-cultured breast cancer cells (MDA-MB-231) with either confluent or sub-confluent bone-marrow-derived MSCs (BM-MSCs); in addition, we treated various tumor cells with conditioned media (CM) obtained from either confluent or sub-confluent BM-MSCs. The results showed that the growth of tumor cells co-cultured with confluent BM-MSCs or treated with CM obtained from confluent BM-MSCs was inhibited, and this effect was significantly stronger than that seen with tumor cells co-cultured with sub-confluent BM-MSCs or CM obtained from sub-confluent BM-MSCs. Subcutaneous tumor formation was completely prevented by the inoculation of tumor cells mixed with CM. In the future, soluble anti-tumor effectors, produced by confluent MSCs, may be used as cell-free therapeutics; this approach provides a solution to current concerns associated with cell-based therapies. |
format | Online Article Text |
id | pubmed-10486504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104865042023-09-09 Autocrine Factors Produced by Mesenchymal Stem Cells in Response to Cell–Cell Contact Inhibition Have Anti-Tumor Properties Chen, Jerry P. Li, Rong Jiang, Jean X. Chen, Xiao-Dong Cells Article Recently, mesenchymal stem cell (MSC) therapies have been questioned as MSCs are capable of both promoting and inhibiting tumorigenesis. Both MSCs and tumor cells replicate to increase their population size; however, MSCs, but not tumor cells, stop dividing when they reach confluence due to cell–cell contact inhibition and then differentiate. We hypothesized that contact inhibition results in the production of effector molecules by confluent MSCs and these effectors are capable of suppressing tumor cell growth. To test this hypothesis, we co-cultured breast cancer cells (MDA-MB-231) with either confluent or sub-confluent bone-marrow-derived MSCs (BM-MSCs); in addition, we treated various tumor cells with conditioned media (CM) obtained from either confluent or sub-confluent BM-MSCs. The results showed that the growth of tumor cells co-cultured with confluent BM-MSCs or treated with CM obtained from confluent BM-MSCs was inhibited, and this effect was significantly stronger than that seen with tumor cells co-cultured with sub-confluent BM-MSCs or CM obtained from sub-confluent BM-MSCs. Subcutaneous tumor formation was completely prevented by the inoculation of tumor cells mixed with CM. In the future, soluble anti-tumor effectors, produced by confluent MSCs, may be used as cell-free therapeutics; this approach provides a solution to current concerns associated with cell-based therapies. MDPI 2023-08-26 /pmc/articles/PMC10486504/ /pubmed/37681882 http://dx.doi.org/10.3390/cells12172150 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Jerry P. Li, Rong Jiang, Jean X. Chen, Xiao-Dong Autocrine Factors Produced by Mesenchymal Stem Cells in Response to Cell–Cell Contact Inhibition Have Anti-Tumor Properties |
title | Autocrine Factors Produced by Mesenchymal Stem Cells in Response to Cell–Cell Contact Inhibition Have Anti-Tumor Properties |
title_full | Autocrine Factors Produced by Mesenchymal Stem Cells in Response to Cell–Cell Contact Inhibition Have Anti-Tumor Properties |
title_fullStr | Autocrine Factors Produced by Mesenchymal Stem Cells in Response to Cell–Cell Contact Inhibition Have Anti-Tumor Properties |
title_full_unstemmed | Autocrine Factors Produced by Mesenchymal Stem Cells in Response to Cell–Cell Contact Inhibition Have Anti-Tumor Properties |
title_short | Autocrine Factors Produced by Mesenchymal Stem Cells in Response to Cell–Cell Contact Inhibition Have Anti-Tumor Properties |
title_sort | autocrine factors produced by mesenchymal stem cells in response to cell–cell contact inhibition have anti-tumor properties |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486504/ https://www.ncbi.nlm.nih.gov/pubmed/37681882 http://dx.doi.org/10.3390/cells12172150 |
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