Membrane protein glycosylation and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan

The adhesion of tumour cells to the hyaluronan (HA) pericellular coat of me sothelial cells is an important step in the peritoneal spread of ovarian ca ncer. Previously, we have shown that the cell surface molecule CD44 is invo lved in this process. Paradoxically, the degree of adhesion does not appear to be related to the amount of CD44 expressed. In order to explain this ob servation we have examined the in vitro adhesion to HA of four high CD44-ex pressing ovarian cancer lines in relation to their CD44 spliced variant con tent and the CD44 glycosylation. Adhesion was measured in multiwell plates coated with different concentrations of HA in order to determine both the a vidity and the maximum adhesion. Two lines had high adhesion and two lines had low adhesion. The avidity for HA was different for each line, but in al l cases this could be totally blocked by treatment with an anti-CD44 antibo dy. The standard form of CD44 was the major species detected by RT/PCR in a ll lines and spliced variants were present in low amounts. Neuraminidase tr eatment increased the adhesion of the 'low-adhesion' lines at all HA coatin g concentrations; but only substantially increased the adhesion of the 'hig h-adhesion' lines at the lower HA coating concentrations. Tunicamycin treat ment decreased the adhesion of the 'high-adhesion lines' at all HA coating concentrations and only substantially decreased the adhesion of one of the 'low-adhesion' lines when the plates were coated with a low concentration o f HA. The adhesion of the remaining 'low-adhesion' line was slightly increa sed after tunicamycin treatment. It is concluded that glycosylation and not spliced variant content of CD44 affects the adhesive properties of ovarian tumour cells. This conclusion may have important consequences for developi ng new therapies in ovarian cancer.