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

Abstract 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 attenuat...

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Autores principales:	Yona Goldshmit, Rita Perelroizen, Alex Yakovchuk, Evgeni Banyas, Lior Mayo, Sari David, Amit Benbenishty, Pablo Blinder, Moshe Shalom, Angela Ruban
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/200f4725602145f4a7fbf82cf2089aa6
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spelling	oai:doaj.org-article:200f4725602145f4a7fbf82cf2089aa62021-12-02T17:57:15ZBlood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo10.1038/s41598-021-94183-82045-2322https://doaj.org/article/200f4725602145f4a7fbf82cf2089aa62021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94183-8https://doaj.org/toc/2045-2322Abstract 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.Yona GoldshmitRita PerelroizenAlex YakovchukEvgeni BanyasLior MayoSari DavidAmit BenbenishtyPablo BlinderMoshe ShalomAngela RubanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yona Goldshmit Rita Perelroizen Alex Yakovchuk Evgeni Banyas Lior Mayo Sari David Amit Benbenishty Pablo Blinder Moshe Shalom Angela Ruban Blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo
description	Abstract 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.
format	article
author	Yona Goldshmit Rita Perelroizen Alex Yakovchuk Evgeni Banyas Lior Mayo Sari David Amit Benbenishty Pablo Blinder Moshe Shalom Angela Ruban
author_facet	Yona Goldshmit Rita Perelroizen Alex Yakovchuk Evgeni Banyas Lior Mayo Sari David Amit Benbenishty Pablo Blinder Moshe Shalom Angela Ruban
author_sort	Yona Goldshmit
title	Blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo
title_short	Blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo
title_full	Blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo
title_fullStr	Blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo
title_full_unstemmed	Blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo
title_sort	blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/200f4725602145f4a7fbf82cf2089aa6
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Blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo

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