Primary Appointment

Metastases are the result of interactions between tumor cells and tissue environments mediated through cell-to-cell and cell-to-matrix contacts and through the release of cytokines and growth factors. My laboratory has developed several models of breast cancer metastasis in nude mice, which can be used for investigating patterns of gene expression underlying the malignant phenotype and as pre-clinical models for testing new therapies.  These include a model for growth of breast cancer cells in the bone of nude mice.   The breast cancer xenograft models are being used to test a tyrosine kinase inhibitor of VEGFR-2 and other kinases.  The pre-clinical work is focused on the “triple-negative” type of breast cancer, which generally responds poorly to standard forms of therapy.

Breast cancer metastases are commonly found in bone and the brain. Although it is well known that breast cancers can metastasize to the brain and bone, relatively little is known about how these metastases form and the phenotypes of breast cancers that grow in these organ environments. Without such information, the rational design of new therapies to prevent or control the growth of metastases is impossible. In large part, the progress in understanding the biology of breast cancer metastasis has been limited by the lack of suitable cell lines and experimental models. For the brain metastasis model, we focus on the role of angiogenic factors, including vascular endothelial growth factor, and use a model of injection of cells in the intra-carotid artery or the left heart to simulate dissemination to the brain. Working to test the hypothesis that breast cancer cells that survive and grow in the brain are unique populations, we established a variant of a human breast cancer cell line by selection of cells from experimental brain metastases.  This variant has significantly enhanced potential for growth in the brain of nude mice, compared with the original cells.  Gene expression microarray analyses were performed to identify genes differentially expressed in the brain-metastasis derived variant.  Current experiments are testing the contributions of genes identified in the microarray analyses to the ability of breast cancer cells to metastasize to brain in the experimental model.

Last updated: 9/22/2009