title: Cysteine-rich protein 61 suppresses cell invasion via down-regulation of matrix metalloproteinase-7 expression in the human gastric carcinoma cell line MKN-45.
abstract: Cysteine-rich protein 61 (CYR61) is a member of the CCN (CYR61/CTGF/NOV) family, which is associated with progression in a variety of human cancers. Our previous study confirmed that the expression levels of CYR61 protein were decreased in gastric carcinoma compared to non-tumoral mucosa as determined by proteome analysis. Histological research also showed that the reduction in CYR61 expression was significantly correlated with cellular invasiveness and inversely correlated with matrix metalloproteinase-7 (MMP-7/matrilysin) expression in human gastric carcinoma. We examined the cause of CYR61 down-regulation in a human gastric carcinoma cell line, MKN-45. Lower expression of CYR61, but no genetic or epigenetic alterations of the gene, were observed. We then examined the correlation between CYR61 protein and MMP-7 expression and cellular invasiveness in MKN-45 cells. CYR61 was secreted from CYR61 expression-vector-transfected 293T cells, and the supernatant was added to MKN-45 cells. The expression level of MMP-7 was reduced by treatment of the supernatant, including CYR61, in a dose-dependent manner. An invasion assay showed that the cellular invasiveness of MKN-45 was significantly suppressed by the transfection of CYR61 expression vector compared to transfection with a control vector. Taken together, these results raise the possibility that CYR61 suppresses cell invasion at least partly via the down-regulation of MMP-7 expression in human gastric carcinoma cells.
authors.affiliation: Division of Molecular Genetics and Biofunction, Department of Biomedical Science, Tottori University Graduate School of Medical Science, Tottori University, Tottori 683-8503, Japan. osamitsu@med.tottori-u.ac.jp.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Osaki
authors.forename: Aiko
authors.initials: A
authors.lastname: Inaba
authors.forename: Kei
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Yui
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Kohei
authors.initials: K
authors.lastname: Shomori
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Inoue
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
authors.forename: Hisao
authors.initials: H
authors.lastname: Ito