Metastasis is the leading cause of death in cancer patients. Understanding the interaction between components of the brain microenvironment and circulating tumor cells is important for understanding how brain metastases develop. The main focus of my current research project will be quantifying the response of microglia to circulating tumor cells in the brain vasculature. Microglia are the first cells that respond to brain tumors when tumor cells infiltrate the initial brain invasion barriers such as endothelial cells. Inflammation caused by cancer cells arrest in vasculature is believed to recruit microglia to the tumor site and secrete cytokines, growth factors, and enzymes that facilitate cancer proliferation. These microglia have been found to be in the vicinity of the tumors in in vitro experiments; my project aims to image the spatio-temporal dynamics of the microglia cells in vivo through a cranial window on mice. Fluorescently labeled B16-F10 melanoma cells which metastasize to brain and prostate RM1 cells which preferentially metastasize to bone, will be injected into the internal carotid artery after the craniotomy. Using two-photon microscopy, circulating tumor cells that have arrested in the brain vasculature will be tracked and the response of microglia to the cells will be quantified. The brain will also be excised and histologically analyzed to detect ICAM and VCAM. The imaging of the metastatic sites will shed light on the dynamic between circulating tumors cells, microglia, and resulting inflammation.
