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Syndecan-2 functions as a docking receptor for pro-matrix metalloproteinase-7 in human colon cancer cells
Heui-Young Ryu1, Jiseon Lee, Sanghwa Yang
1Department of Life Sciences, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750.
Abstract:
Although elevated syndecan-2 expression is known to be crucial for the tumorigenic activity in colon carcinoma cells, how syndecan-2 regulates colon cancer is unclear. In human colon adenocarcinoma tissue samples, we found that both mRNA and protein expression of syndecan-2 were increased, compared with the neighboring normal epithelium, suggesting that syndecan-2 plays functional roles in human colon cancer cells. Consistent with this notion, syndecan-2-overexpressing HT-29 colon adenocarcinoma cells showed enhanced migration/invasion, anchorage-independent growth, and primary tumor formation in nude mice, paralleling their morphological changes into highly tumorigenic cells. In addition, our experiments revealed that syndecan-2 enhanced both expression and secretion of matrix metalloproteinase-7 (MMP-7), directly interacted with pro-MMP-7, and potentiated the enzymatic activity of pro-MMP-7 by activating its processing into the active MMP-7. Collectively, these data strongly suggest that syndecan-2 functions as a docking receptor for pro-MMP-7 in colon cancer cells.
Insights
Syndecan-2 is elevated in colon cancer, promoting tumor growth and spread. It acts as a docking receptor, activating matrix metalloproteinase-7 (MMP-7) to enhance cancer cell invasion and tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Elevated syndecan-2 expression is linked to tumorigenic activity in colon carcinoma.
- The precise regulatory mechanisms of syndecan-2 in colon cancer remain unclear.
Purpose of the Study:
- To investigate the functional roles and molecular mechanisms of syndecan-2 in human colon cancer.
- To elucidate the relationship between syndecan-2 and matrix metalloproteinase-7 (MMP-7) in colon adenocarcinoma.
Main Methods:
- Analysis of syndecan-2 mRNA and protein expression in human colon adenocarcinoma tissues and adjacent normal epithelium.
- Assessment of cellular behaviors (migration, invasion, anchorage-independent growth) in syndecan-2-overexpressing HT-29 cells.
- Investigation of syndecan-2 interaction with pro-matrix metalloproteinase-7 (pro-MMP-7) and its enzymatic activation.
Main Results:
- Syndecan-2 mRNA and protein levels were significantly increased in colon adenocarcinoma tissues compared to normal epithelium.
- Syndecan-2 overexpression in HT-29 cells led to enhanced migration, invasion, anchorage-independent growth, and increased primary tumor formation in vivo.
- Syndecan-2 was found to enhance both the expression and secretion of MMP-7, directly interact with pro-MMP-7, and potentiate its activation to mature MMP-7.
Conclusions:
- Syndecan-2 plays a significant role in promoting the tumorigenicity of human colon cancer cells.
- Syndecan-2 functions as a docking receptor for pro-MMP-7, facilitating its activation and contributing to colon cancer progression.
- Targeting syndecan-2 may represent a therapeutic strategy for colon cancer treatment.
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