Hyaluronan knockdown mice: application to analysis of hyaluronan-mediated pathophysiology

Abstract

Hyaluronan is a ubiquitous, major component of the extracellular matrix. It is involved in cell adhesion and locomotion, and hence in tumor metastasis. We have previously reported that 4-methylumbelliferone (MU) inhibits hyaluronan synthesis and may be a useful tool for examining the functions of hyaluronan. We here demonstrate that MU-mediated inhibition of hyaluronan expression results in suppression of adhesion and locomotion of cultured melanoma cells. Furthermore, MU-treated melanoma cells showed both decreased cell surface hyaluronan formation and suppression of liver metastasis after injection into the mice. Oral administration of MU to mice also decreased tissue hyaluronan content. These hyaluronan knock-down mice displayed suppressed metastasis. Thus, both cell surface hyaluronan of melanoma cells and recipient hyaluronan can promote metastasis, indicating that MU has potential as an anti-metastatic agent.