Elucidating the role of thrombosis and inflammation in breast cancer metastasis

Division Of Basic Sciences - Nci

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Abstract

Objective 1; To identify the mechanisms by which asymptomatic small strokes promote breast cancer brain metastasis. Among all the metastasis, brain metastasis has the worst survival outcomes. It is reported that 10-20% of general population have asymptomatic small strokes found incidentally by MRI. To mimic this clinical scenario in patients with cancer, we have developed a novel stroke-brain metastasis mouse model in which PBS with microthrombi prepared ex vivo by mixing fresh murine blood and thrombin is injected into a common carotid artery (stroke group) on Day 0 followed by intracardiac cancer cell injection on Day 2 in immunocompetent mice. The size and number of the brain metastatic foci were significantly larger in stroke group compared to control group (Injection of PBS without microthrombi). The ASP for further investigation is currently under ACUC review. Objective 2: To determine the mechanisms by which DVT promotes breast cancer growth. DVT is the most common type of venous thromboembolisms in the patients with cancer. In collboration with Dr. Yogen Kanthi from NHLBI who has well-established Electrolytic Inferior Vena Cava Model (EIM) DVT mouse mode, we are dveloping a novel DVT-breast cancer mouse model. We hypothesize that DVT promotes breast cancer growth by altering the innate immunity in bone marrow based on a report that myocardial infarction (local ischemia in heart) reprogrammed Ly6Chi monocytes in the bone marrow to an immunosuppressive phenotype leading to tumor growth. The ASP for this study is currently waiting for final signoffs from ACUC committee members.