We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The Oncolytic Activity of Myxoma Virus against Soft Tissue Sarcoma Is Mediated by the Overexpression of Ribonucleotide Reductase.
- Authors
Yanghee Woo; Warner, Susanne G.; Geha, Rula; Stanford, Marianne M.; Decarolis, Penelope; Rahman, Masmudur M.; Singer, Samuel; McFadden, Grant; Yuman Fong
- Abstract
BACKGROUND: Myxoma virus (MYXV) is an oncolytic poxvirus that lacks the gene for 1 of the subunits of ribonucleotide reductase (RR), a crucial DNA synthesis and repair enzyme. The overexpression of RR has been implicated in the invasiveness of several cancers, including soft tissue sarcomas (STS). The purpose of the study was to investigate the oncolytic efficacy of MYXV in STS with different levels of RR expression. METHODS: The oncolytic effect of recombinant MYXV was evaluated in 4 human STS cell lines, LS141 (a dedifferentiated liposarcoma), DDLS8817 (a dedifferentiated liposarcoma), RDD2213 (recurrent dedifferentiated liposarcoma), and HSSYII (a synovial sarcoma) using infectivity and cytotoxicity assays. Following the overexpression of RRM2 by cDNA transfection and silencing of RRM2 by siRRM2 in these STS cell lines, the RRM2 expression levels were analyzed by Western blot. RESULTS: We observed a direct correlation between viral oncolysis and RRM2 mRNA levels (R=0.96) in STS. Higher RRM2 expression was associated with a more robust cell kill. Silencing the RRM2 gene led to significantly greater cell survival (80%) compared with the control group (P = .003), whereas overexpression of the RRM2 increased viral oncolysis by 33% (P < .001). CONCLUSIONS: Our results show that the oncolytic effects of MYXV correlate directly with RR expression levels and are enhanced in STS cell lines with naturally occurring or artificially induced high expression levels of RR. Myxoma virus holds promise in the treatment of advanced soft tissue cancer, especially in tumors overexpressing RR.
- Subjects
IN vitro studies; WESTERN immunoblotting; APOPTOSIS; GENE expression; CELL survival; MESSENGER RNA; GENE expression profiling; DESCRIPTIVE statistics; OXIDOREDUCTASES; CELL lines; TUMOR markers; ONCOLYTIC virotherapy; DNA viruses; SARCOMA; LIPOSARCOMA
- Publication
Clinical Medicine Insights: Oncology, 2021, Vol 15, p1
- ISSN
1179-5549
- Publication type
Article
- DOI
10.1177/1179554921993069