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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Evidence for increased activated metalloproteinase 2 (MMP-2a) expression associated with human prostate cancer
1Department of Pathology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Abstract:
Immunolabeling studies have previously indicated that increased expression of the 72-kDa matrix metalloproteinase 2 (MMP-2) is associated with human prostate cancer progression. It is not known if the enzymatically active MMP-2 is expressed in prostate cancer and if increased expression is associated with progression. Monoclonal antibodies specific for the activated MMP-2 molecule (MMP-2a, 66 kDa) were used (along with previously developed MMP-2 antibodies) to investigate the expression of MMP-2a and MMP-2 in human prostate tissue extracts. SDS-PAGE, Western blots, and zymography indicated that MMP-2a expression was undetectable in normal prostate (n = 6), benign prostatic hyperplasia (n = 9), and in prostate cancer of low Gleason score (GS) 4 (n = 11). MMP-2a was expressed in prostate cancer of increased GS (n = 37) and in lymph node metastases (n = 7). Quantitative ELISAs of human prostate cancer tissue extracts revealed that the levels of MMP-2 and MMP-2a per microgram of protein increased in prostate cancer tissues of increased GS (n = 48). MMP-2a levels were also high in prostatic lymph node metastases, but MMP-2 was not expressed or was barely detectable in these tissues. The molar ratios of MMP-2a to MMP-2 increased from 0 to 6.23 in tissues of GS 4 to 10, respectively. We conclude that significant increases in MMP-2a are associated with the malignant progression of prostate cancer and with tumor cell metastases to lymph nodes.
Insights
Activated matrix metalloproteinase 2 (MMP-2a) is linked to prostate cancer advancement. Increased MMP-2a expression correlates with higher Gleason scores and lymph node metastasis in prostate cancer patients.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Previous studies suggest a link between matrix metalloproteinase 2 (MMP-2) expression and prostate cancer progression.
- The expression of enzymatically active MMP-2 (MMP-2a) in prostate cancer and its association with disease progression remain unclear.
Purpose of the Study:
- To investigate the expression of activated MMP-2 (MMP-2a) in human prostate tissues.
- To determine if MMP-2a expression is associated with prostate cancer progression and metastasis.
Main Methods:
- Utilized monoclonal antibodies specific for MMP-2a.
- Employed SDS-PAGE, Western blots, zymography, and quantitative ELISAs on normal prostate, benign prostatic hyperplasia, and prostate cancer tissue extracts.
- Analyzed tissues from varying Gleason scores and lymph node metastases.
Main Results:
- MMP-2a was undetectable in normal prostate, benign prostatic hyperplasia, and low Gleason score (GS) 4 prostate cancer.
- MMP-2a was detected in higher GS prostate cancer and lymph node metastases.
- Levels of both MMP-2 and MMP-2a increased with higher GS; MMP-2a was prominent in metastases while MMP-2 was not.
Conclusions:
- Significant increases in activated MMP-2 (MMP-2a) are associated with malignant progression in prostate cancer.
- Elevated MMP-2a levels correlate with tumor cell metastasis to lymph nodes in prostate cancer.
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