The Department of Biomedicine

BBB Seminar: Frits Alan Thorsen

My sabbatical year 2011-2012: Animal models to study brain metastasis

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Frits Alan Thorsen
Department of Biomedicine, University of Bergen

Metastatic brain tumors are the most frequently occurring intracranial neoplasms in adults, with an estimated annual incidence of 200.000 in the US. The frequency is increasing, both due to more effective control of the primary disease, and due to earlier detection using improved imaging modalities. Although we are beginning to understand tumorigenesis and the spread of systemic cancer, the key challenge is still to determine the major mechanisms responsible for malignant disbursement of tumor cells from the primary site to the brain. Providing a better insight into the signaling pathways related to metastatic spread of these tumors may lead to new therapeutic targets and better anticancer strategies. For this purpose we have developed a new animal model to study melanoma metastasis, using human melanoma brain metastatic cells injected into the left cardiac ventricle of nod/scid mice. The model recapitulates metastatic spread seen in the clinic, and by pre-labeling the tumor cells with iron oxide particles, we have been able to track single tumor cells within the brain. Currently, therapeutic and genetic studies are ongoing, and will be presented in the talk.

Efficient drug delivery to brain metastases is difficult due to an often intact blood-brain barrier (BBB) around smaller lesions. Relevant experimental brain metastatic models are thus needed to study biological mechanisms and therapeutic responses of early brain lesions in relation to the BBB. Little is known regarding at which time point in experimental brain metastasis development the BBB is disrupted, and to what extent larger sized molecules at that time are able to penetrate tumor tissue. We have addressed these issues by performing imaging studies, after injecting contrast agents of various molecular weights into an established melanoma brain metastasis model. The results of this study will be presented in the talk.

Chair: Rolf Bjerkvig, Department of Biomedicine