title: Matrilysin as a target for chemotherapy for colon cancer: use of antisense oligonucleotides as antimetastatic agents.
abstract: Matrilysin (MMP-7) is the smallest member of the matrix metalloproteinase (MMP) family. It is frequently expressed in various types of cancer including colon, stomach, prostate, and brain cancers. Previous studies have suggested that matrilysin plays important roles in the progression and metastasis of colon cancer. Recently, we have examined the effects of a matrilysin-specific antisense phosphorothioate oligodeoxyribonucleotide on in vitro invasion and liver metastasis in nude mice of two human colon carcinoma cell lines (CaR-1 and WiDr). In culture, the antisense oligonucleotide effectively inhibited both the secretion of matrilysin by CaR-1 cells and their in vitro invasion through a reconstituted basement membrane. In a nude mouse model, the antisense oligonucleotide potently suppressed the experimental liver metastasis of WiDr cells from the spleen. These results suggest that matrilysin has an important role in the liver metastasis of human colon cancer and that matrilysin antisense oligonucleotides have therapeutic potential for the prevention of metastasis.
authors.affiliation: Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Japan. miyazaki@yokohama-cu.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Miyazaki
authors.forename: N
authors.initials: N
authors.lastname: Koshikawa
authors.forename: S
authors.initials: S
authors.lastname: Hasegawa
authors.forename: N
authors.initials: N
authors.lastname: Momiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Nagashima
authors.forename: K
authors.initials: K
authors.lastname: Moriyama
authors.forename: Y
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.forename: M
authors.initials: M
authors.lastname: Mitsuhashi
authors.forename: H
authors.initials: H
authors.lastname: Shimada
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology*; D006801:Humans; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*
chemical_list: D016376:Oligonucleotides, Antisense; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7