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Literature DB >> 17349582

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 Mutlu¹, 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.

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.

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Year: 2007 PMID： 17349582 PMCID： PMC2180156 DOI： 10.1016/j.ccr.2007.01.015

Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743

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