Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Jerry P., Li, Rong, Jiang, Jean X., Chen, Xiao-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785103022167162880
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
work_keys_str_mv AT chenjerryp autocrinefactorsproducedbymesenchymalstemcellsinresponsetocellcellcontactinhibitionhaveantitumorproperties
AT lirong autocrinefactorsproducedbymesenchymalstemcellsinresponsetocellcellcontactinhibitionhaveantitumorproperties
AT jiangjeanx autocrinefactorsproducedbymesenchymalstemcellsinresponsetocellcellcontactinhibitionhaveantitumorproperties
AT chenxiaodong autocrinefactorsproducedbymesenchymalstemcellsinresponsetocellcellcontactinhibitionhaveantitumorproperties