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Published on: March 30, 2022
Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer
1The Key Laboratory of Bioactive Materials, Ministry of Education, Institute for Molecular Biology, Nankai University, Tianjin 300071, P.R. China. zhangju@nankai.edu.cn
Background:
The type IV collagenases/gelatinases matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) play an important role in cancer invasion and metastasis. In the present study, we measured the expression of mRNAs and enzymatic activities of MMP-9 and -2 in prostate tissues and serum samples from men with or without prostate cancer.
Methods:
A total of 44 tissue samples (three from healthy volunteers, 21 from patients with benign prostate hyperplasia, 10 from patients with localized prostate cancer and 10 from patients with metastatic disease) and 71 serum samples were collected (20 from healthy volunteers, 26 from patients with benign prostatic hyperplasia, 10 from patients with localized cancer, 15 from patients with metastatic cancer). The level of mRNA for MMP-2 and -9 was determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The enzymatic activity of MMPs was determined by zymography.
Results:
Expression of MMP-9 mRNA was significantly higher in malignant than in nonmalignant prostate tissues (P < 0.001), while no significant difference of MMP-2 expression was detected in different prostate tissues. Results of zymography showed that there was significant difference in the enzymatic activity of MMP-9, but not MMP-2, among normal prostate, BPH, localized and metastatic prostate cancer tissues, serum samples (P < 0.05). The active form of MMP-2, with a molecular mass of 62 kDa, was detected in normal prostate, BPH and prostate cancer tissues, but not in the serum samples. Moreover, there was a significant difference in the ratio of the active form (62 kDa) and proform (72 kDa) of MMP-2 among normal, BPH and prostate cancer tissues. This ratio was further increased in metastatic prostate cancer tissues.
Conclusion:
The activity of MMP-9 and the ratio of active form/proform of MMP-2 are associated with the progression and metastasis of prostate cancer.
Insights
Matrix metalloproteinase-9 (MMP-9) activity and the ratio of active to proform matrix metalloproteinase-2 (MMP-2) are linked to prostate cancer progression. These biomarkers show potential for understanding cancer metastasis.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, are implicated in cancer invasion and metastasis.
- Prostate cancer progression involves complex molecular changes affecting tissue remodeling.
Purpose of the Study:
- To investigate the expression and activity of MMP-2 and MMP-9 in prostate tissues and serum.
- To correlate MMP-2 and MMP-9 levels with prostate cancer presence and metastatic status.
Main Methods:
- Analysis of mRNA levels for MMP-2 and MMP-9 using RT-PCR in prostate tissue samples.
- Assessment of MMP enzymatic activity via zymography in tissue and serum samples.
- Comparison of MMP expression and activity across healthy, benign prostatic hyperplasia (BPH), localized, and metastatic prostate cancer groups.
Main Results:
- MMP-9 mRNA expression was significantly elevated in malignant prostate tissues compared to non-malignant tissues.
- MMP-9 enzymatic activity differed significantly across normal, BPH, localized, and metastatic prostate cancer tissues and serum.
- The ratio of active to proform MMP-2 was significantly altered in prostate cancer tissues, increasing with metastatic progression.
Conclusions:
- Elevated MMP-9 activity and a specific MMP-2 active/proform ratio are associated with prostate cancer progression and metastasis.
- These MMP markers may serve as indicators for prostate cancer advancement and metastatic potential.
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