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Effects of microcystin-LR exposure on matrix metalloproteinase-2/-9 expression and cancer cell migration
Zongyao Zhang1, Xu-Xiang Zhang, Wendi Qin
1State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046, China.
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.
Insights
Chronic exposure to microcystin-LR (MC-LR) increases matrix metalloproteinases (MMPs) in the liver and stimulates cancer cell migration. This study highlights potential risks associated with MC-LR contamination.
Area of Science:
- Environmental toxicology
- Molecular biology
- Cancer research
Background:
- Microcystin-LR (MC-LR) is a common cyanotoxin with potential health impacts.
- Matrix metalloproteinases (MMPs) are enzymes involved in tissue remodeling and cancer progression.
- Understanding MC-LR's effects on MMPs and cell migration is crucial for risk assessment.
Purpose of the Study:
- To investigate the impact of chronic MC-LR exposure on hepatic MMP expression.
- To determine MC-LR's effect on the migration of breast cancer cells.
- To elucidate the relationship between MC-LR, MMPs, and cancer cell motility.
Main Methods:
- Oral administration of MC-LR to male mice for 270 days.
- Histopathological examination of liver tissues.
- Immunohistochemical staining, ELISA, and quantitative RT-PCR for MMP-2/-9 expression analysis.
- In vitro culture of MDA-MB-435s breast cancer cells with MC-LR and wound healing assays.
Main Results:
- MC-LR exposure led to hepatic lymphocyte infiltration and fatty degeneration in mice.
- MC-LR significantly up-regulated hepatic MMP-2/-9 expression and mRNA levels.
- MC-LR exposure stimulated breast cancer cell migration in a time- and dose-dependent manner.
- Increased cellular MMP-2/-9 expression was observed in MC-LR-treated cancer cells.
Conclusions:
- Chronic MC-LR exposure alters hepatic MMP-2/-9 expression.
- MC-LR can stimulate cancer cell migration, potentially through MMP modulation.
- These findings suggest a potential mechanism for MC-LR's role in cancer progression.
