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The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

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Related Experiment Video

Updated: Jun 21, 2026

Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion

Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion

Published on: October 20, 2016

Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion.

D S Markovic¹, K Vinnakota, S Chirasani

¹Cellular Neuroscience, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.

Proceedings of the National Academy of Sciences of the United States of America

|July 21, 2009

Summary

Glioma cell invasion, a cause of poor outcomes, is driven by microglial MT1-MMP. Inhibiting microglial activation pathways significantly reduces glioma expansion in preclinical models.

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Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells

Published on: November 28, 2015

Area of Science:

Neuro-oncology
Cellular Biology
Immunology

Background:

Malignant gliomas are aggressive brain tumors with poor patient outcomes.
Glioma cell infiltration into normal brain tissue is a major cause of treatment failure.
Metalloproteases facilitate glioma invasion by degrading the extracellular matrix.

Purpose of the Study:

To investigate the role of membrane type 1 metalloprotease (MT1-MMP) in glioma cell invasion.
To identify the cellular source and regulatory mechanisms of MT1-MMP in the glioma microenvironment.
To evaluate the therapeutic potential of targeting MT1-MMP-mediated pathways in glioma.

Main Methods:

Analysis of MT1-MMP expression in glioma-associated microglia and glioma cells.
Investigating the signaling pathways (toll-like receptors, p38 MAPK) regulating MT1-MMP in microglia.
Utilizing ex vivo models with MT1-MMP-deficient brain tissue and in vivo models with microglia depletion.

Main Results:

MT1-MMP is upregulated in glioma-associated microglia, not glioma cells.
Glioma-released factors activate microglial MT1-MMP via toll-like receptors and the p38 MAPK pathway.
Microglial MT1-MMP activates pro-MMP-2, promoting glioma expansion.
MyD88 deficiency or microglia depletion significantly attenuated glioma expansion in vivo.

Conclusions:

Microglia-derived MT1-MMP plays a critical role in promoting glioma invasion and expansion.
Targeting microglial activation pathways, such as those involving MyD88 and p38 MAPK, represents a promising therapeutic strategy for malignant gliomas.