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

English version

Autoři: Julian Naipauer ^aff001; Santas Rosario ^aff001; Sachin Gupta ^aff001; Courtney Premer ^aff003; Omayra Méndez-Solís ^aff001; Mariana Schlesinger ^aff001; Virginia Ponzinibbio ^aff001; Vaibhav Jain ^aff004; Lauren Gay ^aff004; Rolf Renne ^aff004; Ho Lam Chan ^aff005; Lluis Morey ^aff005; Daria Salyakina ^aff001; Martin Abba ^aff002; Sion Williams ^aff002; Joshua M. Hare ^aff003; Pascal J. Goldschmidt-Clermont ^aff001; Enrique A. Mesri ^aff001
Působiště autorů: Tumor Biology Program, Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research, Department of Microbiology and Immunology, Miami, Florida, United States of America ^aff001; UM-CFAR/ Sylvester CCC Argentina Consortium for Research and Training in Virally induced AIDS-Malignancies, Miami, Florida, United States of America ^aff002; Interdisciplinary Stem Cell Institute; University of Miami Miller School of Medicine, Miami, Florida, United States of America ^aff003; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America ^aff004; Department of Human Genetics, Universidad Nacional de La Plata, La Plata, Argentina ^aff005; Centro de Investigaciones Inmunológicas Básicas y Aplicadas, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina ^aff006; Neurology Basic Science Division, Sylvester Comprehensive Cancer Center; University of Miami Miller School of Medicine, Miami, Florida, United States of America ^aff007
Vyšlo v časopise: PDGFRA defines the mesenchymal stem cell Kaposi’s sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008221
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008221

Souhrn

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.

Klíčová slova:

Carcinogenesis – Endothelial cells – Fluorescence imaging – Gene expression – Kaposi's sarcoma-associated herpesvirus – Mesenchymal stem cells – Kaposi sarcoma – Oncogenic signaling

Zdroje

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