Pathogenesis and Blood-Brain Barrier Heterogeneity of Breast Cancer Brain Metastasis
Final rept. 1 Jul 2004-30 Jun 2005
M D ANDERSON CANCER CENTER HOUSTON TX
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The purpose of this study was to elucidate the pathogenesis of breast cancer brain metastasis and the role of the BBB in the process. Green fluorescent protein GFP expressing breast cancer cells were injected into the left ventricle of nude mice and the progression of brain metastases analyzed. Our data revealed that i 80 hematogenous metastatic cells homing in the brain extravasated and grew along blood vessels ii 20 metastatic cells attached to the microvessel wall did not extravasate immediately but proliferate within the vasculature, this leads to thrombosis-like complications such as infarction of brain parenchyma iii the cancerous thrombus can serve as a sustained releasing source of tumor cells to the downstream area through blood flow, making the spread of tumor cells extremely quick iv continuing intravascular tumor expansion led to disruption of blood vessels and BBB integrity v the overflowing metastatic cells proliferate and migrate along the host vasculature perivascularly to far distant sites and regain the protection of the BBB. vi function of BBE is heterogeneous in different regions of tumor mass. These observations provide rationales for early diagnosis and treatment and improve our understanding of the role of BBB in chemotherapy of brain tumors.
- Anatomy and Physiology
- Medicine and Medical Research