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

Julian Naipauer; Santas Rosario; Sachin Gupta; Courtney Premer; Omayra Méndez-Solís; Mariana Schlesinger; Virginia Ponzinibbio; Vaibhav Jain; Lauren Gay; Rolf Renne; Ho Lam Chan; Lluis Morey; Daria Salyakina; Martin Abba; Sion Williams; Joshua M Hare; Pascal J Goldschmidt-Clermont; Enrique A Mesri

doi:10.1371/journal.ppat.1008221

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

Journal article

Open access

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

Julian Naipauer, Santas Rosario, Sachin Gupta, Courtney Premer, Omayra Méndez-Solís, Mariana Schlesinger, Virginia Ponzinibbio, Vaibhav Jain, Lauren Gay, Rolf Renne, …

PLoS pathogens, Vol.15(12), pp.e1008221-e1008221

2019-12

DOI: https://doi.org/10.1371/journal.ppat.1008221

PMCID: PMC6980685

PMID: 31881074

Appears in UM Open Access Research Published in PloS

Abstract

Animals

Receptor, Platelet-Derived Growth Factor alpha - metabolism

Gene Expression - physiology

Mesenchymal Stem Cells - cytology

Herpesvirus 8, Human - genetics

Signal Transduction - physiology

Mice

Sarcoma, Kaposi - virology

Neovascularization, Pathologic - virology

Mesenchymal Stem Cells - virology

Carcinogenesis - metabolism

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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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.130 Lymphomas; 1.130.1220 Kaposi
Web Of Science research areas: Microbiology; Parasitology; Virology
ESI research areas: Microbiology

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Title: PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
Creators: Julian Naipauer - UM-CFAR/ Sylvester CCC Argentina Consortium for Research and Training in Virally induced AIDS-Malignancies, Miami, Florida, United States of America
Santas Rosario - Tumor Biology Program, Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research, Department of Microbiology and Immunology, Miami, Florida, United States of America
Sachin Gupta - Tumor Biology Program, Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research, Department of Microbiology and Immunology, Miami, Florida, United States of America
Courtney Premer - Interdisciplinary Stem Cell Institute; University of Miami Miller School of Medicine, Miami, Florida, United States of America
Omayra Méndez-Solís - Tumor Biology Program, Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research, Department of Microbiology and Immunology, Miami, Florida, United States of America
Mariana Schlesinger - Tumor Biology Program, Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research, Department of Microbiology and Immunology, Miami, Florida, United States of America
Virginia Ponzinibbio - UM-CFAR/ Sylvester CCC Argentina Consortium for Research and Training in Virally induced AIDS-Malignancies, Miami, Florida, United States of America
Vaibhav Jain - Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America
Lauren Gay - Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America
Rolf Renne - Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America
Ho Lam Chan - Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida, United States of America
Lluis Morey - Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida, United States of America
Daria Salyakina - Tumor Biology Program, Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research, Department of Microbiology and Immunology, Miami, Florida, United States of America
Martin Abba - Centro de Investigaciones Inmunológicas Básicas y Aplicadas, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
Sion Williams - Neurology Basic Science Division, Sylvester Comprehensive Cancer Center; University of Miami Miller School of Medicine, Miami, Florida, United States of America
Joshua M Hare - Interdisciplinary Stem Cell Institute; University of Miami Miller School of Medicine, Miami, Florida, United States of America
Pascal J Goldschmidt-Clermont - Tumor Biology Program, Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research, Department of Microbiology and Immunology, Miami, Florida, United States of America
Enrique A Mesri - UM-CFAR/ Sylvester CCC Argentina Consortium for Research and Training in Virally induced AIDS-Malignancies, Miami, Florida, United States of America
Publication Details: PLoS pathogens, Vol.15(12), pp.e1008221-e1008221
Publisher: United States
Grant note: P30 CA240139 / NCI NIH HHS
Academic Unit: Leadership Department; Miller School of Medicine; Interdisciplinary Stem Cell Institute; Microbiology and Immunology Research; UMMG Department of Neurology; UMMG Dept of Human Genetics - Clinical and Translational Genetics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 31881074
PMCID: PMC6980685
Record Identifier: 991031578733202976