Over expression of CD44V8-10 in human bladder cancer cells decreases their interaction with hyaluronic acid and potentiates their malignant progression.

Abstract

We evaluated the effects of the over expression of CD44v8-10, one of the high molecular form of CD44, on the malignant potential of UM-UC-3 human bladder cancer cells in vitro and in vivo. We introduced CD44v8-10 complementary DNA into UM-UC-3 cells, which do not express detectable level of CD44v8-10 protein, and generated the CD44v8-10 over expressing cell line UM-UC-3/v8-10 and the vector only transfected cell line UM-UC-3/C. The effects of the introduction of CD44v8-10 into UM-UC-3 cells on the ability to bind hyaluronic acid (HA) were analyzed by the cell adhesion assay and the cell migration assay. We then evaluated tumor progression of UM-UC-3 sublines after subcutaneous and orthotopic injection into athymic nude mice. There were no significant differences in in vitro growth rates. UM-UC-3/v8-10 cells showed significantly decreased binding and migration ability to HA but not to other extracellular matrix proteins. Furthermore, UM-UC-3/v8-10 cells demonstrated significantly increased tumor growth after subcutaneous as well as orthotopic injection into athymic nude mice and enhanced lymph node metastasis after orthotopic injection compared with UM-UC-3/C cells. These findings suggest that CD44v8-10 over expression in human bladder cancer cells decreases their interaction with HA and potentiates their malignant progression.