An in vitro model for studying cellular transformation by Kaposi sarcoma herpesvirus

Shane C. McAllister, Ryan S. Hanson, Kyleen N. Grissom, Sara Botto, Ashlee V. Moses

Research output: Contribution to journalArticle

Abstract

Kaposi sarcoma (KS) is an unusual tumor composed of proliferating spindle cells that is initiated by infection of endothelial cells (EC) with KSHV, and develops most often in the setting of immunosuppression. Despite decades of research, optimal treatment of KS remains poorly defined and clinical outcomes are especially unfavorable in resource-limited settings. KS lesions are driven by pathological angiogenesis, chronic inflammation, and oncogenesis, and various in vitro cell culture models have been developed to study these processes. KS arises from KSHV-infected cells of endothelial origin, so EC-lineage cells provide the most appropriate in vitro surrogates of the spindle cell precursor. However, because EC have a limited in vitro lifespan, and as the oncogenic mechanisms employed by KSHV are less efficient than those of other tumorigenic viruses, it has been difficult to assess the processes of transformation in primary or telomerase-immortalized EC. Therefore, a novel EC-based culture model was developed that readily supports transformation following infection with KSHV. Ectopic expression of the E6 and E7 genes of human papillomavirus type 16 allows for extended culture of age-and passage-matched mock-and KSHV-infected EC and supports the development of a truly transformed (i.e., tumorigenic) phenotype in infected cell cultures. This tractable and highly reproducible model of KS has facilitated the discovery of several essential signaling pathways with high potential for translation into clinical settings.

Original languageEnglish (US)
Article numbere54828
JournalJournal of Visualized Experiments
Volume2017
Issue number126
DOIs
StatePublished - Aug 2017

Keywords

  • Biology
  • Endothelial cell
  • Issue 126
  • KSHV
  • Kaposi sarcoma
  • Oncogenesis
  • Primary effusion lymphoma
  • Transformation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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