An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus

Shane C McAllister, Ryan L. 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)
JournalJournal of visualized experiments : JoVE
Issue number126
DOIs
StatePublished - Aug 25 2017
Externally publishedYes

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Kaposi's Sarcoma
Herpesviridae
Endothelial cells
Human Herpesvirus 8
Endothelial Cells
Cell culture
Cell Culture Techniques
Pathologic Neovascularization
Telomerase
Human papillomavirus 16
Viruses
Cell Lineage
Infection
In Vitro Techniques
Tumors
Immunosuppression
Genes
Carcinogenesis
Inflammation
Phenotype

Cite this

An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus. / McAllister, Shane C; Hanson, Ryan L.; Grissom, Kyleen N.; Botto, Sara; Moses, Ashlee V.

In: Journal of visualized experiments : JoVE, No. 126, 25.08.2017.

Research output: Contribution to journalArticle

McAllister, Shane C ; Hanson, Ryan L. ; Grissom, Kyleen N. ; Botto, Sara ; Moses, Ashlee V. / An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus. In: Journal of visualized experiments : JoVE. 2017 ; No. 126.
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