| Title | In vivo-restricted and reversible malignancy induced by human herpesvirus-8 KSHV: a cell and animal model of virally induced Kaposi's sarcoma. |
| Publication Type | Journal Article |
| Year of Publication | 2007 |
| Authors | Mutlu AD'Agostino, Cavallin LE, Vincent L, Chiozzini C, Eroles P, Duran EM, Asgari Z, Hooper AT, La Perle KMD, Hilsher C, Gao S-J, Dittmer DP, Rafii S, Mesri EA |
| Journal | Cancer Cell |
| Volume | 11 |
| Issue | 3 |
| Pagination | 245-58 |
| Date Published | 2007 Mar |
| ISSN | 1535-6108 |
| Keywords | Angiopoietins, Animals, Antigens, Viral, Bone Marrow Cells, Cell Lineage, Cell Transformation, Neoplastic, Cell Transformation, Viral, Cells, Cultured, Chromosomes, Artificial, Bacterial, Disease Models, Animal, Endothelial Cells, Herpesvirus 8, Human, Humans, Membrane Glycoproteins, Mice, Mice, Nude, Neovascularization, Pathologic, Nuclear Proteins, Sarcoma, Kaposi, Vascular Endothelial Growth Factor A |
| 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. |
| DOI | 10.1016/j.ccr.2007.01.015 |
| Alternate Journal | Cancer Cell |
| PubMed ID | 17349582 |
| PubMed Central ID | PMC2180156 |
| Grant List | R01 CA109232 / CA / NCI NIH HHS / United States R01 CA163217 / CA / NCI NIH HHS / United States R01 CA096512 / CA / NCI NIH HHS / United States R01 DE018304-03 / DE / NIDCR NIH HHS / United States R01 CA124332 / CA / NCI NIH HHS / United States R01 DE018304 / DE / NIDCR NIH HHS / United States CA096512 / CA / NCI NIH HHS / United States CA110136 / CA / NCI NIH HHS / United States CA109232 / CA / NCI NIH HHS / United States R01 CA109232-05 / CA / NCI NIH HHS / United States R01 DE018304-02 / DE / NIDCR NIH HHS / United States R01 CA132637 / CA / NCI NIH HHS / United States R01 CA075918 / CA / NCI NIH HHS / United States R01 DE018304-01 / DE / NIDCR NIH HHS / United States R03 CA110136 / CA / NCI NIH HHS / United States CA075918 / CA / NCI NIH HHS / United States |