title: Matrilysin (MMP-7) induces homotypic adhesion of human colon cancer cells and enhances their metastatic potential in nude mouse model.
abstract: 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.
authors.affiliation: Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, 641-12 Maioka-cho, Totsuka-ku, Yokohama 244-0813, Japan.
authors.forename: Mitomu
authors.initials: M
authors.lastname: Kioi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Shouichi
authors.initials: S
authors.lastname: Higashi
authors.forename: Naohiko
authors.initials: N
authors.lastname: Koshikawa
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D015820:Cadherins / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects*; D002449:Cell Aggregation / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis
chemical_list: D015820:Cadherins; D020783:Matrix Metalloproteinase 7