Enhanced tumorigenicity of fibroblasts transformed with human herpesvirus 8 chemokine receptor vGPCR by successive passage in nude and immunocompetent mice

Item Type:	Article
Title:	Enhanced tumorigenicity of fibroblasts transformed with human herpesvirus 8 chemokine receptor vGPCR by successive passage in nude and immunocompetent mice
Creators Name:	Thirunarayanan, N. and Cifire, F. and Fichtner, I. and Posner, S. and Benga, J. and Reiterer, P. and Kremmer, E. and Koelble, K. and Lipp, M.
Abstract:	The human herpes virus 8 (HHV-8)-encoded G protein-coupled chemokine receptor (vGPCR) has been implicated in the pathogenesis of Kaposi's sarcoma (KS), particularly because of its high constitutive signaling activity. Here, we used retroviral transduction to generate vGPCR-expressing 3T3 fibroblasts that are tumorigenic in nude mice, but as expected fail to induce tumors in their immunocompetent counterparts. However, tumor fragments obtained from nude mice grow progressively in immunocompetent BALB/c mice. Unexpectedly, vGPCR-expressing cells established from grafted tumor fragments gave rise to tumors in immunocompetent mice. These tumors exhibit a striking histological resemblance to KS including plump spindle cell morphology, a high degree of vascularization and brisk mitotic activity. High expression of vGPCR was confirmed in the cell lines and tumors using a newly developed vGPCR-specific monoclonal antibody. Finally, short interfering RNA directed at vGPCR abrogated or significantly delayed tumorigenesis in mice, demonstrating that the tumor development is specifically driven by vGPCR. This novel model for vGPCR-mediated oncogenesis will contribute to our understanding of the role of vGPCR in the pathogenesis of HHV-8 and may even be important in identifying critical molecular and epigenetic changes during tumor progression in vivo.
Keywords:	Chemokine Receptor, vGPCR, Kaposi's Sarcoma, Animal Model, HHV-8, Animals, Cricetinae, Mice
Source:	Oncogene
ISSN:	0950-9232
Publisher:	Nature Publishing Group
Volume:	26
Number:	39
Page Range:	5702-5712
Date:	23 August 2007
Official Publication:	https://doi.org/10.1038/sj.onc.1210357
PubMed:	View item in PubMed

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