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Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) on prostate cancer cell lines
O Nagakawa1, K Murakami, T Yamaura
1Department of Pathogenic Biochemistry, Institute of Natural Medicine, 930-0194, Toyama, Japan.
Abstract:
Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase, which activates proMMP-2 and expressed on the cell surface in many invasive cancer cells. We investigated the expression of MT1-MMP in prostate cancer cell lines. MT1-MMP protein and mRNA were expressed in PC-3, DU-145 and TSU-pr1 cells (androgen-independent prostate cancer cell lines), but in LNCaP cells (androgen-dependent prostate cancer cell line). MT1-MMP protein was negative and mRNA was low to detect by RT-PCR. Cell lysate of PC-3 cleaved proMMP-2 to the active form. In addition, both hepatocyte growth factor (HGF) and gastrin-releasing peptide (GRP) increased Matrigel invasion and induced the expression of MT1-MMP protein in DU-145 prostate cancer cells. These results suggest that MT1-MMP is indeed the tumor-specific activator of proMMP-2 in androgen-independent prostate cancer cells and plays an important role in the invasive properties of prostate cancer cells.
Insights
Membrane-type metalloproteinase-1 (MT1-MMP) activates proMMP-2 in invasive prostate cancer. MT1-MMP expression correlates with androgen-independent prostate cancer cell invasion, suggesting its role in tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Membrane-type metalloproteinase-1 (MT1-MMP) is a cell surface enzyme crucial for extracellular matrix remodeling.
- MT1-MMP activates proMMP-2, a key enzyme implicated in cancer invasion and metastasis.
- Understanding MT1-MMP expression in prostate cancer is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the expression patterns of MT1-MMP in various prostate cancer cell lines.
- To determine the role of MT1-MMP in the invasive potential of prostate cancer cells.
- To explore the influence of growth factors on MT1-MMP expression and invasion.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) to detect MT1-MMP mRNA.
- Western blotting to assess MT1-MMP protein levels.
- Matrigel invasion assays to evaluate cell invasiveness.
Main Results:
- MT1-MMP protein and mRNA were significantly expressed in androgen-independent prostate cancer cell lines (PC-3, DU-145, TSU-pr1).
- LNCaP cells (androgen-dependent) showed minimal MT1-MMP expression.
- PC-3 cell lysates activated proMMP-2, and hepatocyte growth factor (HGF) and gastrin-releasing peptide (GRP) enhanced MT1-MMP expression and invasion in DU-145 cells.
Conclusions:
- MT1-MMP is a tumor-specific activator of proMMP-2 in androgen-independent prostate cancer.
- MT1-MMP expression is closely linked to the invasive properties of prostate cancer cells.
- Targeting MT1-MMP may represent a therapeutic strategy for invasive prostate cancer.