Blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo.

Autor: Goldshmit Y; Steyer School of Health Professions, Sackler Faculty of Medicine, Tel-Aviv University, P.O. Box 39040, 6997801, Tel Aviv, Israel.; Australian Regenerative Medicine Institute, Monash Biotechnology, 15 Innovation Walk, Clayton, VIC, 3800, Australia., Perelroizen R; Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, 6997801, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, 6997801, Tel Aviv, Israel., Yakovchuk A; Steyer School of Health Professions, Sackler Faculty of Medicine, Tel-Aviv University, P.O. Box 39040, 6997801, Tel Aviv, Israel., Banyas E; Steyer School of Health Professions, Sackler Faculty of Medicine, Tel-Aviv University, P.O. Box 39040, 6997801, Tel Aviv, Israel., Mayo L; Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, 6997801, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, 6997801, Tel Aviv, Israel., David S; Steyer School of Health Professions, Sackler Faculty of Medicine, Tel-Aviv University, P.O. Box 39040, 6997801, Tel Aviv, Israel., Benbenishty A; Department of Biological Regulation, Weizmann Institute of Science, 7610001, Rehovot, Israel., Blinder P; Sagol School of Neuroscience, Tel Aviv University, 6997801, Tel Aviv, Israel.; Neurobiology Department, George S. Wise Faculty of Life Sciences, Tel Aviv University, 6997801, Tel Aviv, Israel., Shalom M; Steyer School of Health Professions, Sackler Faculty of Medicine, Tel-Aviv University, P.O. Box 39040, 6997801, Tel Aviv, Israel., Ruban A; Steyer School of Health Professions, Sackler Faculty of Medicine, Tel-Aviv University, P.O. Box 39040, 6997801, Tel Aviv, Israel. angellruban@tauex.tau.ac.il.; Sagol School of Neuroscience, Tel Aviv University, 6997801, Tel Aviv, Israel. angellruban@tauex.tau.ac.il.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Jul 19; Vol. 11 (1), pp. 14644. Date of Electronic Publication: 2021 Jul 19.
DOI: 10.1038/s41598-021-94183-8
Abstrakt: Inhibition of extracellular glutamate (Glu) release decreases proliferation and invasion, induces apoptosis, and inhibits melanoma metastatic abilities. Previous studies have shown that Blood-glutamate scavenging (BGS), a novel treatment approach, has been found to be beneficial in attenuating glioblastoma progression by reducing brain Glu levels. Therefore, in this study we evaluated the ability of BGS treatment to inhibit brain metastatic melanoma progression in-vivo. RET melanoma cells were implanted in C56BL/6J mice to induce brain melanoma tumors followed by treatment with BGS or vehicle administered for fourteen days. Bioluminescent imaging was conducted to evaluate tumor growth, and plasma/CSF Glu levels were monitored throughout. Immunofluorescence staining of Ki67 and 53BP1 was used to analyze tumor cell proliferation and DNA double-strand breaks. In addition, we analyzed CD8, CD68, CD206, p-STAT1 and iNOS expression to evaluate alterations in tumor micro-environment and anti-tumor immune response due to treatment. Our results show that BGS treatment reduces CSF Glu concentration and consequently melanoma growth in-vivo by decreasing tumor cell proliferation and increasing pro-apoptotic signaling in C56BL/6J mice. Furthermore, BGS treatment supported CD8 + cell recruitment and CD68 + macrophage invasion. These findings suggest that BGS can be of potential therapeutic relevance in the treatment of metastatic melanoma.
(© 2021. The Author(s).)
Databáze: MEDLINE
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