The aim of this current study was to examine the significance of CD44 expression in mediating
cancer cell adhesion to human bone marrow endothelial cell(s) (hBMEC). Differential CD44 expression on two metastatic
prostate cancer cell lines, PC3 (CD44 +ve) and DU145 (CD44 -ve) and four
breast cancer cell lines was confirmed by immunoblotting and immunocytochemistry. In cell adhesion assays, PC3 but not DU145 cells demonstrated a rapid adhesion to hBMECs. Treatment of PC3 cells with a
neutralizing antibody against CD44 standard (CD44s) and CD44 splice variants decreased PC3 cell adhesion to hBMECs. Similarly, depletion of CD44 expression using RNA interference decreased the ability of PC3 cells and two CD44 +ve
breast cancer cell lines (MDA-MB-231 and MDA-MB-157) to bind
FITC-conjugated
hyaluronan (
FITC-HA) and to adhere to hBMECs. In contrast, transfection of DU145 cells or the T47D and MCF-7
breast cancer cell lines to express CD44s increased cell surface binding of
FITC-HA and cell adherence to hBMECs. Treatment of PC3 and MDA-MD-231 cells but not hBMECs with
hyaluronidase attenuated cell adhesion, suggesting that cell surface expression of CD44 on prostate and
breast cancer cells may promote the retention of a HA coat that facilitates their initial arrest on bone marrow endothelium.