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.
PubMed ID
36863485
Volume
15
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). School of Medicine Faculty Publications. 955.
https://digitalscholar.lsuhsc.edu/som_facpubs/955
10.1016/j.tvr.2023.200259