In Vivo-Restricted and Reversible Malignancy Induced by Human Herpesvirus-8 KSHV: A Cell and Animal Model of Virally Induced Kaposi's Sarcoma

Agata D.Agostino Mutlu, Lucas E. Cavallin, Loïc Vincent, Chiara Chiozzini, Pilar Eroles, Elda M. Duran, Zahra Asgari, Andrea T. Hooper, Krista M.D. La Perle, Chelsey Hilsher, Shou Jiang Gao, Dirk P. Dittmer, Shahin Rafii, Enrique A. Mesri

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120 Scopus citations

Abstract

Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial-lineage cells generates a cell (mECK36) that forms KS-like tumors in mice. mECK36 expressed most KSHV genes and were angiogenic, but they didn't form colonies in soft agar. In nude mice, mECK36 formed KSHV-harboring vascularized spindle cell sarcomas that were LANA+/podoplanin+, overexpressed VEGF and Angiopoietin ligands and receptors, and displayed KSHV and host transcriptomes reminiscent of KS. mECK36 that lost the KSHV episome reverted to nontumorigenicity. siRNA suppression of KSHV vGPCR, an angiogenic gene upregulated in mECK36 tumors, inhibited angiogenicity and tumorigenicity. These results show that KSHV malignancy is in vivo growth restricted and reversible, defining mECK36 as a biologically sensitive animal model of KSHV-dependent KS.

Original languageEnglish (US)
Pages (from-to)245-258
Number of pages14
JournalCancer Cell
Volume11
Issue number3
DOIs
StatePublished - Mar 13 2007

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Mutlu, A. D. A., Cavallin, L. E., Vincent, L., Chiozzini, C., Eroles, P., Duran, E. M., Asgari, Z., Hooper, A. T., La Perle, K. M. D., Hilsher, C., Gao, S. J., Dittmer, D. P., Rafii, S., & Mesri, E. A. (2007). In Vivo-Restricted and Reversible Malignancy Induced by Human Herpesvirus-8 KSHV: A Cell and Animal Model of Virally Induced Kaposi's Sarcoma. Cancer Cell, 11(3), 245-258. https://doi.org/10.1016/j.ccr.2007.01.015