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Kaposi sarcoma-associated herpesvirus (KSHV) induces a functional tumor-associated phenotype for oral fibroblasts. - PubMed - NCBI
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Cancer Lett. 2012 May 28;318(2):214-20. doi: 10.1016/j.canlet.2011.12.019. Epub 2011 Dec 17.

Kaposi sarcoma-associated herpesvirus (KSHV) induces a functional tumor-associated phenotype for oral fibroblasts.

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1
Department of Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, United States.

Abstract

The Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), the most common HIV/AIDS-associated tumor worldwide. Involvement of the oral cavity portends a poor prognosis for patients with KS, but mechanisms for KSHV regulation of the oral tumor microenvironment are largely unknown. Infiltrating fibroblasts are found with KS lesions, and KSHV establishes latent infection within human primary fibroblasts in vitro, but contributions for KSHV-infected fibroblasts to the KS microenvironment have not been previously characterized. Secretion of pro-migratory factors and intratumoral invasion are characteristics of tumor-associated fibroblasts (TAF) found in the microenvironment of non-viral malignancies. In the present study, we show that latent KSHV infection of primary human fibroblasts isolated from the oral cavity enhances their secretion of KS-promoting cytokines and intrinsic invasiveness through VEGF-dependent mechanisms. Moreover, we find that KSHV induces these effects through Sp1- and Egr2-dependent transcriptional activation of the Extracellular Matrix MetalloPRoteinase INducer (emmprin). These data implicate KSHV activation of emmprin in the induction of a "TAF-like" phenotype for oral fibroblasts in the KS microenvironment and support the potential utility of targeting TAFs and/or emmprin in the treatment of oral KS.

PMID:
22186301
PMCID:
PMC3303930
DOI:
10.1016/j.canlet.2011.12.019
[Indexed for MEDLINE]
Free PMC Article
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