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...

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Detalles Bibliográficos
Autores: Naipauer, Julian, Rosario, Santas, Gupta, Sachin, Premer, Courtney, Méndez-Solís, Omayra, Schlesinger, Mariana, Ponzinibbio, María 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 J., Mesri, Enrique A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Institución:Universidad Nacional de La Plata
Repositorio:SEDICI (UNLP)
Idioma:inglés
OAI Identifier:oai:sedici.unlp.edu.ar:10915/107504
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107504
Access Level:acceso abierto
Palabra clave:Biología
Ciencias Médicas
Mesenchymal stem cells
Gene expression
Cancers and neoplasms
Carcinogenesis
Kaposi sarcoma
Descripción
Sumario: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.

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