Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer

Bone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptos...

Descripción completa

Detalles Bibliográficos
Autores principales: McGuire, Jeremy J., Frieling, Jeremy S., Lo, Chen Hao, Li, Tao, Muhammad, Ayaz, Lawrence, Harshani R., Lawrence, Nicholas J., Cook, Leah M., Lynch, Conor C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851397/
https://www.ncbi.nlm.nih.gov/pubmed/33526787
http://dx.doi.org/10.1038/s41467-021-20962-6
_version_ 1783645619005423616
author McGuire, Jeremy J.
Frieling, Jeremy S.
Lo, Chen Hao
Li, Tao
Muhammad, Ayaz
Lawrence, Harshani R.
Lawrence, Nicholas J.
Cook, Leah M.
Lynch, Conor C.
author_facet McGuire, Jeremy J.
Frieling, Jeremy S.
Lo, Chen Hao
Li, Tao
Muhammad, Ayaz
Lawrence, Harshani R.
Lawrence, Nicholas J.
Cook, Leah M.
Lynch, Conor C.
author_sort McGuire, Jeremy J.
collection PubMed
description Bone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rates in bone. Acquired resistance to apoptosis is PCa cell intrinsic, and is associated with a shift in IL-28Rα signaling via STAT1 to STAT3. Notably, STAT3 ablation or inhibition impairs MSC-selected prostate cancer cell growth and survival. Thus, bone marrow MSCs drive the emergence of therapy-resistant bone metastatic prostate cancer yet this can be disabled by targeting STAT3.
format Online
Article
Text
id pubmed-7851397
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-78513972021-02-08 Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer McGuire, Jeremy J. Frieling, Jeremy S. Lo, Chen Hao Li, Tao Muhammad, Ayaz Lawrence, Harshani R. Lawrence, Nicholas J. Cook, Leah M. Lynch, Conor C. Nat Commun Article Bone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rates in bone. Acquired resistance to apoptosis is PCa cell intrinsic, and is associated with a shift in IL-28Rα signaling via STAT1 to STAT3. Notably, STAT3 ablation or inhibition impairs MSC-selected prostate cancer cell growth and survival. Thus, bone marrow MSCs drive the emergence of therapy-resistant bone metastatic prostate cancer yet this can be disabled by targeting STAT3. Nature Publishing Group UK 2021-02-01 /pmc/articles/PMC7851397/ /pubmed/33526787 http://dx.doi.org/10.1038/s41467-021-20962-6 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
McGuire, Jeremy J.
Frieling, Jeremy S.
Lo, Chen Hao
Li, Tao
Muhammad, Ayaz
Lawrence, Harshani R.
Lawrence, Nicholas J.
Cook, Leah M.
Lynch, Conor C.
Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer
title Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer
title_full Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer
title_fullStr Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer
title_full_unstemmed Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer
title_short Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer
title_sort mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851397/
https://www.ncbi.nlm.nih.gov/pubmed/33526787
http://dx.doi.org/10.1038/s41467-021-20962-6
work_keys_str_mv AT mcguirejeremyj mesenchymalstemcellderivedinterleukin28drivestheselectionofapoptosisresistantbonemetastaticprostatecancer
AT frielingjeremys mesenchymalstemcellderivedinterleukin28drivestheselectionofapoptosisresistantbonemetastaticprostatecancer
AT lochenhao mesenchymalstemcellderivedinterleukin28drivestheselectionofapoptosisresistantbonemetastaticprostatecancer
AT litao mesenchymalstemcellderivedinterleukin28drivestheselectionofapoptosisresistantbonemetastaticprostatecancer
AT muhammadayaz mesenchymalstemcellderivedinterleukin28drivestheselectionofapoptosisresistantbonemetastaticprostatecancer
AT lawrenceharshanir mesenchymalstemcellderivedinterleukin28drivestheselectionofapoptosisresistantbonemetastaticprostatecancer
AT lawrencenicholasj mesenchymalstemcellderivedinterleukin28drivestheselectionofapoptosisresistantbonemetastaticprostatecancer
AT cookleahm mesenchymalstemcellderivedinterleukin28drivestheselectionofapoptosisresistantbonemetastaticprostatecancer
AT lynchconorc mesenchymalstemcellderivedinterleukin28drivestheselectionofapoptosisresistantbonemetastaticprostatecancer

Ejemplares similares