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Quantifying the Brain Metastatic Tumor Micro-Environment using an Organ-On-A Chip 3D Model, Machine Learning, and Confocal Tomography
Published on: August 16, 2020
The brain microenvironment and cancer metastasis
Isaiah J Fidler1, Krishnakumar Balasubramanian, Qingtang Lin
1Department of Cancer Biology, Cancer Metastasis Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. ifidler@mdanderson.org
Molecules and Cells
|August 28, 2010
Summary
Cancer metastasis involves organ-specific interactions. Activated astrocytes in the brain microenvironment protect brain metastases from chemotherapy, contributing to treatment resistance.
Area of Science:
- Oncology
- Neuroscience
- Cancer Biology
Background:
- Metastasis is a complex, multi-step process where cancer cells interact with unique organ microenvironments.
- Brain metastases from lung, breast, and melanoma cancers are often fatal and resistant to therapy.
- The blood-brain barrier presents a challenge, being intact in small metastases and leaky but still protective in larger ones.
Purpose of the Study:
- To investigate the role of the brain microenvironment, specifically astrocytes, in the resistance of brain metastases to chemotherapy.
Main Methods:
- Analysis of the interactions between metastatic cancer cells and the brain microenvironment.
- Examination of the blood-brain barrier's integrity in relation to metastasis size.
- Investigation of astrocyte activation and its effect on tumor cell survival in the presence of chemotherapeutic drugs.
Main Results:
- The organ microenvironment significantly influences cancer cell proliferation, angiogenesis, invasion, and survival.
- Activated astrocytes are found surrounding and infiltrating brain metastases.
- Activated astrocytes were demonstrated to protect tumor cells from chemotherapeutic agents.
Conclusions:
- Activated astrocytes in the brain microenvironment play a protective role for tumor cells against chemotherapy.
- This astrocyte-mediated protection contributes to the therapeutic resistance observed in brain metastases.
- Targeting astrocyte activation may represent a novel therapeutic strategy for brain metastases.
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