Elevated iNOS and 3'-nitrotyrosine in Kaposi's Sarcoma tumors and mouse model.

Autor:	Vladimirova O; The Wistar Institute, Philadelphia, PA, 19104, USA., Soldan S; The Wistar Institute, Philadelphia, PA, 19104, USA., Su C; The Wistar Institute, Philadelphia, PA, 19104, USA., Kossenkov A; The Wistar Institute, Philadelphia, PA, 19104, USA., Ngalamika O; Dermatology and Venereology Section, University Teaching Hospitals, University of Zambia School of Medicine, Lusaka, P.O. Box 50110, Zambia., Tso FY; Department of Interdisciplinary Oncology, Stanley S Scott Cancer Center, State University Health Sciences Center, New Orleans, LA, USA., West JT; Department of Interdisciplinary Oncology, Stanley S Scott Cancer Center, State University Health Sciences Center, New Orleans, LA, USA., Wood C; Department of Interdisciplinary Oncology, Stanley S Scott Cancer Center, State University Health Sciences Center, New Orleans, LA, USA., Lieberman PM; The Wistar Institute, Philadelphia, PA, 19104, USA. Electronic address: Lieberman@wistar.org.
Jazyk:	angličtina
Zdroj:	Tumour virus research [Tumour Virus Res] 2023 Jun; Vol. 15, pp. 200259. Date of Electronic Publication: 2023 Mar 01.
DOI:	10.1016/j.tvr.2023.200259
Abstrakt:	Kaposi's Sarcoma (KS) is a heterogenous, multifocal vascular malignancy caused by the human herpesvirus 8 (HHV8), also known as Kaposi's Sarcoma-Associated Herpesvirus (KSHV). Here, we show that KS lesions express iNOS/NOS2 broadly throughout KS lesions, with enrichment in LANA positive spindle cells. The iNOS byproduct 3-nitrotyrosine is also enriched in LANA positive tumor cells and colocalizes with a fraction of LANA-nuclear bodies. We show that iNOS is highly expressed in the L1T3/mSLK tumor model of KS. iNOS expression correlated with KSHV lytic cycle gene expression, which was elevated in late-stage tumors (>4 weeks) but to a lesser degree in early stage (1 week) xenografts. Further, we show that L1T3/mSLK tumor growth is sensitive to an inhibitor of nitric oxide, L-NMMA. L-NMMA treatment reduced KSHV gene expression and perturbed cellular gene pathways relating to oxidative phosphorylation and mitochondrial dysfunction. These finding suggest that iNOS is expressed in KSHV infected endothelial-transformed tumor cells in KS, that iNOS expression depends on tumor microenvironment stress conditions, and that iNOS enzymatic activity contributes to KS tumor growth. Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paul M. Lieberman is a founder and advisor to Vironika, LLC. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu