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Status |
Public on Jul 14, 2023 |
Title |
KSHV-induced iNOS in Kaposi’s Sarcoma tumors and mouse model |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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 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 tumor growth is sensitive to an inhibitor of nitric oxide, L-NMMA. 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.
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Overall design |
RNA-seq of L1T3 tumors with and without inhibitor of nitric oxide, L-NMMA (NG-methyl L-arginine)
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Contributor(s) |
Vladimirova O, Lieberman P |
Citation(s) |
36863485 |
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Submission date |
Jan 10, 2023 |
Last update date |
Jul 14, 2023 |
Contact name |
Priyankara J Wickramasinghe |
E-mail(s) |
priyaw@wistar.org
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Phone |
2154956837
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Organization name |
The Wistar Institute
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Department |
Bioinformatics
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Lab |
Genomics
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Street address |
3601 Spruce Street
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City |
Philadelphia |
State/province |
PA |
ZIP/Postal code |
19104 |
Country |
USA |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (4)
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Relations |
BioProject |
PRJNA922466 |