In vivo-restricted and reversible malignancy induced by human herpesvirus-8 KSHV: A cell and animal model of virally induced Kaposi's sarcoma

被引：117

作者：

Mutlu, Agata D'Agostino

Cavallin, Lucas E.

Vincent, Loic

Chiozzini, Chiara

Eroles, Pilar

Duran, Elda M.

Asgari, Zahra

Hooper, Andrea T.

La Perle, Krista M. D.

Hilsher, Chelsey

Gao, Shou-Jiang

Dittmer, Dirk P.

Rafii, Shahin

Mesri, Enrique A. ^{[1
]}

机构：

[1] Cornell Univ, Weill Med Coll, Lab Viral Oncogenesis, Div Heamatol Oncol,Dept Med, New York, NY 10021 USA

[2] Cornell Univ, Weill Med Coll, Howard Hughes Med Inst, Dept Med Genet, New York, NY 10021 USA

[3] Cornell Univ, Weill Med Coll, Dept Pathol, New York, NY 10021 USA

[4] Cornell Univ, Weill Med Coll, Lab Med, New York, NY 10021 USA

[5] Univ Miami, Miller Sch Med, Program Viral Oncol, Dept Microbiol & Immunol, Miami, FL 33136 USA

[6] Univ Miami, Miller Sch Med, Program Viral Oncol, Sylvester Canc Ctr, Miami, FL 33136 USA

[7] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

[8] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[9] Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78229 USA

[10] Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78229 USA

[11] Univ Texas, Hlth Sci Ctr, Childrens Canc Res Inst, San Antonio, TX 78229 USA

来源：

CANCER CELL | 2007年 / 11卷 / 03期

关键词：

D O I：

10.1016/j.ccr.2007.01.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：245 / 258

页数：14

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