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Updated: Feb 26, 2026
Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
Glioma sensitive or chemoresistant to temozolomide differentially modulate macrophage protumor activities
Juliana H Azambuja1, Elita F da Silveira2, Taíse R de Carvalho3
1Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brazil; Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Brazil.
Background:
Glioblastomas are the most devastating brain tumor characterized by chemoresistance development and poor prognosis. Macrophages are a component of tumor microenvironment related to glioma malignancy. The relation among inflammation, innate immunity and cancer is accepted; however, molecular and cellular mechanisms mediating this relation and chemoresistance remain unresolved.
Objective:
Here we evaluated whether glioma sensitive or resistant to temozolomide (TMZ) modulate macrophage polarization and inflammatory pathways associated. The impact of glioma-macrophage crosstalk on glioma proliferation was also investigated.
Methods:
GL261 glioma chemoresistance was developed by exposing cells to increasing TMZ concentrations over a period of 6months. Mouse peritoneal macrophages were exposed to glioma-conditioned medium or co-cultured directly with glioma sensitive (GL) or chemoresistant (GLTMZ). Macrophage polarization, in vitro and in vivo glioma proliferation, redox parameters, ectonucleotidase activity and ATP cytotoxicity were performed.
Results:
GLTMZ cells were more effective than GL in induce M2-like macrophage polarization and in promote a strong immunosuppressive environment characterized by high IL-10 release and increased antioxidant potential, which may contribute to glioma chemoresistance and proliferation. Interestingly, macrophage-GLTMZ crosstalk enhanced in vitro and in vivo proliferation of chemoresistant cells, decreased ectonucleotidase activities, which was followed by increased macrophage sensitivity to ATP induced death.
Conclusions:
Results suggest a differential macrophage modulation by GLTMZ cells, which may favor the maintenance of immunosuppressive tumor microenvironment and glioma proliferation.
General Significance:
The induction of immunosuppressive environment and macrophage education by chemoresistant gliomas may be important for tumor recovery after chemotherapy and could be considered to overcome chemoresistance development.
