Effects of microcystin-LR exposure on matrix metalloproteinase-2/-9 expression and cancer cell migration.

ABSTRACT

This study assessed the effects of microcystin-LR (MC-LR) exposure on matrix metalloproteinases (MMPs) expression and cancer cell migration. After male mice were orally administered with different concentrations of MC-LR for 270 d, histopathologic observation revealed an obvious hepatic lymphocyte infiltration or fatty degeneration. Immunohistochemical staining and enzyme-linked immunosorbent assay demonstrated that MC-LR treatment (even at 1 nM) caused up-regulated expressions of hepatic MMP-2/-9. Quantitative reverse-transcriptase PCR showed that the exposure to 80 nM MC-LR induced an increase of MMP-2/-9 mRNA levels by 1.0 and 1.9 fold. Breast cancer cells (MDA-MB-435s) were also cultured with MC-LR solutions and a wound healing assay demonstrated that MC-LR posed a time/dose-dependent stimulation effect on migration of the cancer cells. Gelatin electrophoresis and quantitative PCR showed significant increases in cellular MMP-2/-9 expressions after MC-LR exposure. This study indicated that chronic exposure to MC-LR could alter MMP-2/-9 expressions and stimulate cancer cell migration.