The brain microenvironment and cancer metastasis.
The process of metastasis consists of a series of sequential, selective steps that few cells can complete. The outcome of cancer metastasis depends on multiple interactions between metastatic cells and homeostatic mechanisms that are unique to one or another organ microenvironment. The specific organ microenvironment determines the extent of cancer cell proliferation, angiogenesis, invasion and survival. Many lung cancer, breast cancer, and melanoma patients develop fatal brain metastases that do not respond to therapy. The blood-brain barrier is intact in and around brain metastases that are smaller than 0.25 mm in diameter. Although the blood-brain barrier is leaky in larger metastases, the lesions are resistant to many chemotherapeutic drugs. Activated astrocytes surround and infiltrate brain metastases. The physiological role of astrocytes is to protect against neurotoxicity. Our current data demonstrate that activated astrocytes also protect tumor cells against chemotherapeutic drugs.
Fidler
Isaiah J
IJ
Department of Cancer Biology, Cancer Metastasis Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. ifidler@mdanderson.org
Balasubramanian
Krishnakumar
K
Lin
Qingtang
Q
Kim
Seung Wook
SW
Kim
Sun-Jin
SJ
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000473:pathology; D001812:Blood-Brain Barrier / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000556:secondary*; D004195:Disease Models, Animal; D006801:Humans; D009389:Neovascularization, Pathologic; D059016:Tumor Microenvironment
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