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Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
Increased expression of stress inducible protein 1 in glioma-associated microglia/macrophages
Anna Carolina Carvalho da Fonseca1, Huaqing Wang2, Haitao Fan2
1Laboratório de Morfogênese Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
Abstract:
Factors released by glioma-associated microglia/macrophages (GAMs) play an important role in the growth and infiltration of tumors. We have previously demonstrated that the co-chaperone stress-inducible protein 1 (STI1) secreted by microglia promotes proliferation and migration of human glioblastoma (GBM) cell lines in vitro. In the present study, in order to investigate the role of STI1 in a physiological context, we used a glioma model to evaluate STI1 expression in vivo. Here, we demonstrate that STI1 expression in both the tumor and in the infiltrating GAMs and lymphocytes significantly increased with tumor progression. Interestingly, high expression of STI1 was observed in macrophages and lymphocytes that infiltrated brain tumors, whereas STI1 expression in the circulating blood monocytes and lymphocytes remained unchanged. Our results correlate, for the first time, the expression of STI1 and glioma progression, and suggest that STI1 expression in GAMs and infiltrating lymphocytes is modulated by the brain tumor microenvironment.
Insights
Stress-inducible protein 1 (STI1) expression increases with glioma progression, particularly in tumor-infiltrating immune cells. This suggests STI1 plays a role in the tumor microenvironment’s influence on brain tumor growth.
Area of Science:
- Neuro-oncology
- Immunology
- Molecular Biology
Background:
- Glioma-associated microglia/macrophages (GAMs) release factors influencing tumor growth and infiltration.
- Previous in vitro studies showed stress-inducible protein 1 (STI1) secreted by microglia promotes glioblastoma (GBM) cell proliferation and migration.
Purpose of the Study:
- To investigate the role of STI1 in a physiological context within a glioma model.
- To evaluate in vivo STI1 expression in relation to tumor progression.
Main Methods:
- Utilized a glioma animal model to assess STI1 expression.
- Analyzed STI1 levels in tumor tissue, infiltrating GAMs, lymphocytes, and circulating blood cells.
Main Results:
- STI1 expression significantly increased in both the tumor and infiltrating GAMs and lymphocytes with tumor progression.
- High STI1 expression was observed in macrophages and lymphocytes infiltrating brain tumors.
- STI1 expression in circulating blood monocytes and lymphocytes remained unchanged.
Conclusions:
- STI1 expression correlates with glioma progression.
- STI1 expression in GAMs and infiltrating lymphocytes is modulated by the brain tumor microenvironment.
- STI1 may be a key factor in the tumor microenvironment's impact on glioma.
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