Document Type
Article
Publication Date
6-1-2023
Publication Title
Tumour virus research
Abstract
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.
DOI
10.1016/j.tvr.2023.200259
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Vladimirova, Olga; Soldan, Samantha; Su, Chenhe; Kossenkov, Andrew; Ngalamika, Owen; Tso, For Yue; West, John T.; Wood, Charles; and Lieberman, Paul M., "Elevated iNOS and 3'-nitrotyrosine in Kaposi's Sarcoma tumors and mouse model" (2023). LSU-LCMC Cancer Center Faculty Publications. 49.
https://digitalscholar.lsuhsc.edu/llcc_facpubs/49
10.1016/j.tvr.2023.200259