PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.

Autor: Julian Naipauer, Santas Rosario, Sachin Gupta, Courtney Premer, Omayra Méndez-Solís, Mariana Schlesinger, Virginia Ponzinibbio, Vaibhav Jain, Lauren Gay, Rolf Renne, Ho Lam Chan, Lluis Morey, Daria Salyakina, Martin Abba, Sion Williams, Joshua M Hare, Pascal J Goldschmidt-Clermont, Enrique A Mesri
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS Pathogens, Vol 15, Iss 12, p e1008221 (2019)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1008221
Popis: 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.
Databáze: Directory of Open Access Journals
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