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


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: 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


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Hygiena a epidemiologie Infekční lékařství Laboratoř

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PLOS Pathogens


2019 Číslo 12

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