CD44 variant exon (CD44v) 3 is a heparan sulfate-binding isoform of CD44. The 
role of CD44v3 in invasion and metastasis associated with heparan sulfate in 
colon cancer cell lines and cases of colon cancer was examined. Expression of 
CD44v3 mRNA and protein was observed in five of six human colorectal cancer cell 
lines. Colo320 and WiDr cells expressed CD44v3 at high levels. Heparan sulfate 
treatment increased the invasive activity of Colo320 and WiDr cells to rates 
14.3 and 12.6 times higher, respectively, than that of untreated cells. However, 
heparan sulfate treatment did not affect cell growth. Repression of CD44v3 
protein production by antisense S-oligodeoxynucleotide treatment reduced the 
binding affinities and capacities for heparan sulfate by Colo320 and WiDr cells 
in comparison with that of control cells, and it also reduced the invasiveness 
of both cell lines to one-fifth that of control cells. In heparan 
sulfate-treated Colo320 cells, the levels of CD44v3 protein in the Triton 
X-100-insoluble fraction and moesin-precipitated fraction were increased, 
suggesting that heparan sulfate treatment facilitates association of CD44 
molecules with the cytoskeleton. Immunohistochemical analysis showed CD44v3 to 
be expressed in 21 of 37 (57%) colorectal cancer cases. Positive CD44v3 
expression was associated with more advanced pathological stage and poorer 
prognosis than negative CD44v3 expression. These data support a role for CD44v3 
in invasion and metastasis by colorectal carcinoma cells.