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...

ver descrição completa

Detalhes bibliográficos
Autores: Naipauer, Julian, Rosario, Santas, Gupta, Sachin, Premer, Courtney, Méndez Solís, Omayra, Schlesinger, Mariana, Ponzinibbio, Maria Virginia, Jain, Vaibhav, Gay, Lauren, Renne, Rolf, Chan, Ho Lam, Morey, Lluis, Salyakina, Daria, Abba, Martín Carlos, Williams, Sion, Hare, Joshua M., Goldschmidt Clermont, Pascal, Mesri, Enrique Alfredo
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/126251
Acesso em linha:http://hdl.handle.net/11336/126251
Access Level:acceso abierto
Palavra-chave:KSHV
PDGFRA
Mesenchymal stem cell
Angiogenic environment
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
Descrição
Resumo: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.

Registos relacionados