Antagonistic Action of Hyaluronan Oligomers in Breast Cancer

摘要

The objective of this project is to determine whether hyaluronan interactions are involved in growth and invasion of mammary carcinoma cells inascites. Syngeneic mice were injected intraperitoneally with stable transfectants of TA3/St murine mammary carcinoma cells that overexpress soluble CD44, a hyaluronan-binding protein that would be expected:to compete% with endogenous hyaluronan-protein interactions. The behavior of these transfectants was compared with that of transfectants expressing mutated soluble CD44 that does not bind hyaluronan. Overexpression of soluble cD44, but not mutated%soluble CD44, - inhibited tumor cell growth in ascites as well as invasion of the peritoneal wall. When grown in vitro in soft agar, the soluble CD44 transfectants exhibited a dramatic reduction in colony formation composted to wild type, vector-transfected and mutant soluble CD44-transfected TA3/St cells. Thus, perturbation of hyaluronan interactions by soluble CD44 has a direct effect on the growth characteristics of these tumor cells, leading to inhibition of anchorage independent growth in vitro and ascites growth in vivo.