Kl. Vleminckx et al., ENLARGED CELL-ASSOCIATED PROTEOGLYCANS ABOLISH E-CADHERIN FUNCTIONALITY IN INVASIVE TUMOR-CELLS, Cancer research, 54(4), 1994, pp. 873-877
Mouse and dog epithelial cell lines, expressing high levels of the Ca2
+-dependent cell-cell adhesion molecule E-cadherin in vitro, generated
invasive and metastatic tumors in athymic mice. From these tumors, ne
oplastic cell lines were isolated. All ex vivo isolates retained high
expression levels of E-cadherin at their surface. Nevertheless, some s
howed a fusiform morphotype, were defective in Ca2+-dependent cell agg
regation, and were invasive in vitro, indicating that E-cadherin was n
ot functional. Cell-associated proteoglycans were found to be enlarged
in these variants as compared to their counterparts with functional E
-cadherin. Treatment of the cells with the drug 4-methylumbelliferyl b
eta-D-xyloside specifically reduced the amount and size of cell-associ
ated proteoglycans. This same drug induced an epithelial morphotype, i
ncreased Ca2+- and E-cadherin-dependent cell aggregation, and abrogate
d invasiveness without influencing E-cadherin expression levels. Our r
esults indicate that enlarged proteoglycans can prevent the hemophilic
binding of E-cadherin, probably by steric hindrance. This is one more
mechanism by which carcinomas may counteract invasion-suppressor gene
s and acquire malignancy.