Mechanisms Governing Tumor Invasion and Metastasis in Breast Cancer
A number of factors contribute to tumor invasion and metastasis in breast cancer, including an imbalance of the components of the plasminogen activator system which allows tumor cells to degrade the extracellular matrix (ECM) and metastasize.  PAI-1 is a serine protease inhibitor (serpin) that inhibits urokinase-type plasminogen activator (uPA) from cleaving plasminogen to plasmin, a serine protease which degrades ECM.  Contrary to its role as an inhibitor, elevated levels of PAI-1 alone is indicative of poor prognosis in breast cancer patients.  In addition to PAI-1, breast cancer cell lines have been shown to express PPAR-g, a member of the nuclear receptor superfamily involved in adipocyte differentiation.  PPAR-g has also been shown to be differentially transactivated by omega-3 and omega-6 fatty acids.  Since obesity is a risk factor associated with breast cancer, the relationship between PPAR-g expression and invasive behaviors of breast cancer cells is of interest.  Based upon these observations, my central hypothesis is that certain naturally occurring PPAR-g ligands upregulate PAI-1, uPA, and uPAR in adipocytes and breast cancer cells, and cause changes in the breast tissue microenvironment which promote invasion.  In current studies, I am investigating the effects of PPAR-g transactivation by dietary fatty acids in both adipocytes and breast cancer cells, and the relationship between PPAR-g expression and breast cancer cell invasion in vitro.