Blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo
| Autor: | Angela Ruban, Lior Mayo, Evgeni Banyas, Amit Benbenishty, Yona Goldshmit, Pablo Blinder, Rita Perelroizen, Alex Yakovchuk, Sari David, Moshe Ben Shalom |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oxaloacetic Acid Cancer therapy Science Glutamic Acid Apoptosis Article Metastasis 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Immune system In vivo Cell Line Tumor medicine Tumor Microenvironment Animals Humans Molecular Targeted Therapy Melanoma Cell Proliferation Multidisciplinary CD68 Brain Neoplasms Glutamate receptor medicine.disease Recombinant Proteins Mice Inbred C57BL 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer research Medicine Drug Therapy Combination Glioblastoma CD8 DNA Aspartate Aminotransferase Cytoplasmic Signal Transduction |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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