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Published on: June 23, 2013
Morusin regulates the migration of M2 macrophages and GBM cells through the CCL4-CCR5 axis
Yu Zhao1, Xinying Zhou1, Lei Hong2
1School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230006, China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, China.
Background:
Glioblastoma (GBM) is the most aggressive tumor in the central nervous system. Tumor-associated macrophage (TAMs) represent a major immune cell population in tumor microenvironment (TME) and exert immunosuppressive effects that impede GBM treatment. Morusin is a flavonoid extracted from mulberry trees and has anti-tumor properties against various cancers, including glioma. However, the impact of morusin on the TME of gliomas has not been explored.
Methods:
We evaluated the effect of morusin on the tumor microenvironment using a mouse glioma model through in vivo and in vitro experiments. In vitro experiments demonstrated the effects of morusin on the viability of RAW264.7 and THP1 cells, and the migration ability of M2 macrophages. Furthermore, we investigated the effect of conditioned medium (CM) of morusin-treated M2 macrophages on the migration of glioblastoma cell lines GL261, U87, and U251.
Result:
Morusin alleviated the GBM progression and prolonged mouse survival by inhibiting the ratio of macrophages to CD206+ macrophages. Mechanistically, we demonstrated that morusin could effectively inhibit the secretion of the chemokine CCL4 in M2 macrophage which consequently decreased CCL4-dependent CCR5 activation. This leads to the reduced migration of both macrophages and glioblastoma cells in TME. These findings provide a strong rationale for the development of morusin as a potential therapeutic agent for GBM, either as a standalone treatment or in combination with other immunotherapeutic strategies, and warrant further preclinical and clinical investigations.
Insights
Morusin, a mulberry flavonoid, combats glioblastoma by modulating the tumor microenvironment. It reduces immunosuppressive macrophages and inhibits glioblastoma cell migration, offering a new therapeutic avenue.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor.
- Tumor-associated macrophages (TAMs) in the GBM microenvironment promote immune suppression.
- Morusin, a mulberry flavonoid, shows anti-cancer potential but its effect on glioma TME is unknown.
Purpose of the Study:
- To investigate morusin's impact on the glioblastoma tumor microenvironment (TME).
- To explore morusin's effects on macrophage and glioblastoma cell migration.
Main Methods:
- Utilized a mouse glioma model for in vivo and in vitro studies.
- Assessed morusin's effects on macrophage viability and migration.
- Examined the influence of morusin-treated M2 macrophage conditioned medium on glioblastoma cell lines.
Main Results:
- Morusin inhibited GBM progression and improved mouse survival by altering macrophage populations.
- Morusin suppressed CCL4 chemokine secretion in M2 macrophages, reducing CCL4-dependent CCR5 activation.
- This mechanism decreased the migration of both macrophages and glioblastoma cells within the TME.
Conclusions:
- Morusin effectively modulates the GBM TME by targeting macrophage-mediated immunosuppression.
- The study suggests morusin's potential as a therapeutic agent for GBM, alone or with immunotherapy.
- Further preclinical and clinical studies are warranted to validate morusin's efficacy in GBM treatment.
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