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.

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