Jb. Catterall et al., Membrane protein glycosylation and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan, CLIN EXP M, 17(7), 1999, pp. 583-591
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.