Matrilysin (MMP-7) is thought to contribute to invasive growth and
metastasis of colon
carcinoma and many other human
cancers. The present study demonstrates that treatment of human colon
carcinoma cells with active
matrilysin induces cell aggregation in vitro and promotes liver
metastasis in nude mice. When two kinds of colon
carcinoma cell lines were incubated with active
matrilysin, this
enzyme efficiently bound to the cell surface and induced loose cell aggregation, which led to
E-cadherin-mediated tight cell aggregation. Synthetic
MMP inhibitors inhibited both the membrane binding of
matrilysin and
matrilysin-induced cell aggregation, while
TIMP-2 inhibited only the cell aggregation. Two other active
MMPs,
stromelysin and
gelatinase A, neither bound to cell membrane nor induced cell aggregation.
Tumor cells in loose cell aggregates could reaggregate even after they were freed from
matrilysin and dispersed. When injected into the spleen of nude mice, the
tumor cells in the stable aggregates produced much larger metastatic nodules in the livers than control cells and those in the loose aggregates. These results suggest that
matrilysin may enhance metastatic potential of
tumor cells by processing a
cell surface protein(s) and thereby inducing loose and then tight aggregation of
tumor cells.