PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.
PLoS Pathog
; 15(12): e1008221, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31881074
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcoma de Kaposi
/
Receptor alfa de Fator de Crescimento Derivado de Plaquetas
/
Células-Tronco Mesenquimais
/
Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos