Tumor metastasis to the brain is a relatively frequent occurance in a number of common systemic cancers, however, the prognosis of afflicted patients remains grim despite recent therapeutic advances. This project proposes to examine metastatic brain tumors from mammary carcinoma of human and rat origin, in terms of their biological, pathological, and biochemical properties. An initial focus is to develop a relevant animal metastatic brain tumor model in rat using the 13762NF mammary adenocarcinoma. Preliminary studies have suggested that brain colonizing tumor cell variants are being selected by repeated sequential cycles of inoculating tumor cells into the carotid artery, harvesting the brain tumor nodules and in vitro growth in tissue culture. A major emphasis will be to compare the rat brain metastatic tumor cells to human mammary carcinoma brain lesions and also to the appropriate primary tumor and other distant metastases in other organs. The various possible routes of metastatic spread of the tumor cells in the brain will also be investigated. The various metastatic brain tumor cells will be examined for their biological properties, pathologies, and kariotypes. Furthermore, the cell surface components of tumor cells will be examined to determine if the expression of glycoproteins, proteins, proteoglycans, or glycolipids correlates with their brain colonizing ability. Several cell surface components have been demonstrated to be expressed by both human and rat breast carcinoma cells, and their altered expression may reflect the tumor cells metastatic capabilities. Extension of these results may lead us to new understanding of metastatic brain tumor implantation, growth, and colonization and to new approaches in therapy.
