Mouse models of brain metastasis for unravelling tumour progression

Secondary tumours in the brain account for 40% of triple negative breast cancer patients, and the percentage may be higher at the time of autopsy. The use of in vivo models allow us to recapitulate the molecular mechanisms potentially used by circulating breast tumour cells to proliferate within the brain. Metastasis is a multistep process that depends on the success of several stages including cell evasion from the primary tumour, distribution and survival within the blood stream and cerebral microvasculature, penetration of the blood-brain barrier and proliferation within the brain microenvironment. Cellular adhesion molecules are key proteins involved in all of the steps in the metastatic process. Our group has developed two different in vivo models to encompass both seeding and colonisation stages of the metastatic process: (1) haematogenous dissemination of tumour cells by direct injection into the left ventricle of the heart, and (2) direct implantation of the tumour cells into the mouse brain. This chapter describes, in detail, the practical implementation of the intracerebral model, which can be used to analyse tumour proliferation within a specificarea of the central nervous system and tumour–host cell interactions. We also describe the use of immunohistochemistry techniques to identify, at the molecular scale, tumour–host cell interactions, which may open new windows for brain metastasis therapy.