Role of CD44 in Tumor Progression.

The goal of this research project is to determine how CD44, the cell surface receptor for hyaluronan, stimulates tumor progression. Based upon a variety of evidence, we postulate that CD44 allows tumor cells to degrade hyaluronan which, in turn, increases their vascular supply. During this past year, we have prepared a series of human breast cancer cell lines that have been transfected with a CD44 expression vector. In the immediate future, we will inject these CD44 expressing cells into nude mice and determine if the resulting tumors demonstrate an increased number of endothelial cells as compared to tumors from control cells that do not express CD44. In another set of experiments, we have examined a series of human breast cancer cell lines that differ in their invasive properties MCF 1 0A before and after transfection with the oncogenes c-HA-ras andor c-erbB-2. We found that the expression of the low molecular weight isoform of CD44 85 kDa, but not the high molecular weight isoforms 105-150 kDa, was correlated with the invasive properties of the cells and their ability to bind isotopically labeled hyaluronan. These results suggest that the expression of the 85 kDa isoform of CD44 may be the best marker of hyaluronan binding and degradation, as well as the metastatic behavior of tumor cells.