Author/Authors :
Mutlu، نويسنده , , Agata DʹAgostino and Cavallin، نويسنده , , Lucas E. and Vincent، نويسنده , , Loïc and Chiozzini، نويسنده , , Chiara and Eroles، نويسنده , , Pilar and Duran، نويسنده , , Elda M. and Asgari، نويسنده , , Zahra and Hooper، نويسنده , , Andrea T. and La Perle، نويسنده , , Krista M.D. and Hilsher، نويسنده , , Chelsey and Gao، نويسنده , , Shou-Jiang and Dittmer، نويسنده , , Dirk P. and Rafii، نويسنده , , Shahin and Mesri، نويسنده , , Enrique A.، نويسنده ,
Abstract :
Summary
ection of a Kaposiʹs 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 didnʹt 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.
