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PDGFRA defines the mesenchymal stem cell Kaposi’s sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
Kaposi’s sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as K...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980685/ https://www.ncbi.nlm.nih.gov/pubmed/31881074 http://dx.doi.org/10.1371/journal.ppat.1008221 |
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author | Naipauer, Julian Rosario, Santas Gupta, Sachin Premer, Courtney Méndez-Solís, Omayra Schlesinger, Mariana Ponzinibbio, Virginia Jain, Vaibhav Gay, Lauren Renne, Rolf Chan, Ho Lam Morey, Lluis Salyakina, Daria Abba, Martin Williams, Sion Hare, Joshua M. Goldschmidt-Clermont, Pascal J. Mesri, Enrique A. |
author_facet | Naipauer, Julian Rosario, Santas Gupta, Sachin Premer, Courtney Méndez-Solís, Omayra Schlesinger, Mariana Ponzinibbio, Virginia Jain, Vaibhav Gay, Lauren Renne, Rolf Chan, Ho Lam Morey, Lluis Salyakina, Daria Abba, Martin Williams, Sion Hare, Joshua M. Goldschmidt-Clermont, Pascal J. Mesri, Enrique A. |
author_sort | Naipauer, Julian |
collection | PubMed |
description | Kaposi’s sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis. |
format | Online Article Text |
id | pubmed-6980685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-69806852020-02-07 PDGFRA defines the mesenchymal stem cell Kaposi’s sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment Naipauer, Julian Rosario, Santas Gupta, Sachin Premer, Courtney Méndez-Solís, Omayra Schlesinger, Mariana Ponzinibbio, Virginia Jain, Vaibhav Gay, Lauren Renne, Rolf Chan, Ho Lam Morey, Lluis Salyakina, Daria Abba, Martin Williams, Sion Hare, Joshua M. Goldschmidt-Clermont, Pascal J. Mesri, Enrique A. PLoS Pathog Research Article Kaposi’s sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis. Public Library of Science 2019-12-27 /pmc/articles/PMC6980685/ /pubmed/31881074 http://dx.doi.org/10.1371/journal.ppat.1008221 Text en © 2019 Naipauer et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Naipauer, Julian Rosario, Santas Gupta, Sachin Premer, Courtney Méndez-Solís, Omayra Schlesinger, Mariana Ponzinibbio, Virginia Jain, Vaibhav Gay, Lauren Renne, Rolf Chan, Ho Lam Morey, Lluis Salyakina, Daria Abba, Martin Williams, Sion Hare, Joshua M. Goldschmidt-Clermont, Pascal J. Mesri, Enrique A. PDGFRA defines the mesenchymal stem cell Kaposi’s sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment |
title | PDGFRA defines the mesenchymal stem cell Kaposi’s sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment |
title_full | PDGFRA defines the mesenchymal stem cell Kaposi’s sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment |
title_fullStr | PDGFRA defines the mesenchymal stem cell Kaposi’s sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment |
title_full_unstemmed | PDGFRA defines the mesenchymal stem cell Kaposi’s sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment |
title_short | PDGFRA defines the mesenchymal stem cell Kaposi’s sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment |
title_sort | pdgfra defines the mesenchymal stem cell kaposi’s sarcoma progenitors by enabling kshv oncogenesis in an angiogenic environment |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980685/ https://www.ncbi.nlm.nih.gov/pubmed/31881074 http://dx.doi.org/10.1371/journal.ppat.1008221 |
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