期刊
CLINICAL & EXPERIMENTAL METASTASIS
卷 25, 期 7, 页码 799-810出版社
SPRINGER
DOI: 10.1007/s10585-008-9193-z
关键词
brain metastasis; brain pathology; breast cancer; neuroinflammation; reactive glia; xenograft
类别
资金
- US Department of Defense Breast Cancer Research Program [W81 XWH-062-0033]
- National Cancer Institute
- CCR
- NIH
Interactions between tumor cells and the microenvironment are crucial to tumor formation and metastasis. The central nervous system serves as a sanctuary site for metastasis, resulting in poor prognosis in diagnosed patients. The incidence of brain metastasis is increasing; however, little is known about interactions between the brain and metastatic cells. Brain pathology was examined in an experimental model system of brain metastasis, using a subline of MDA-MB-231 human breast cancer cells. The results were compared with an analysis of sixteen resected human brain metastases of breast cancer. Experimental metastases formed preferentially in specific brain regions, with a distribution similar to clinical cases. In both the 231-BR model, and in human specimens, Ki67 expression indicated that metastases were highly proliferative (similar to 50%). Little apoptosis was observed in either set of tumors. In the model system, metastases elicited a brain inflammatory response, with extensive reactive gliosis surrounding metastases. Similarly, large numbers of glial cells were found within the inner tumor mass of human brain metastases. In vitro co-cultures demonstrated that glia induced a similar to 5-fold increase in metastatic cell proliferation (P < 0.001), suggesting that brain tissue secretes factors conducive to tumor cell growth. Molecules used to signal between tumor cells and the surrounding glia could provide a new avenue of therapeutic targets for brain metastases.
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