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Updated: Oct 4, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
The accumulation of angiostatin-like fragments in human prostate carcinoma
1Department of Anatomic Pathology, Kyushu University, Fukuoka, 812-8582 Japan.
Purpose:
Angiostatin, a potent inhibitor of angiogenesis and, hence, the growth of tumor cell metastasis, is generated by a proteolytic enzyme from plasminogen. However, its localization and specific enzymes have yet to be ascertained in human tissue.
Experimental Design:
To elucidate the generation and the localization of angiostatin in prostate carcinoma, we examined angiostatin generation in a panel of human prostate cancer cell lines and performed immunohistochemistry with the antibodies to angiostatin and prostate-specific antigen (PSA), a potent proteolytic enzyme of angiostatin in 55 cases of prostate carcinoma.
Results:
We demonstrated that the lysates of human prostate carcinoma cell lines could generate angiostatin-like fragments from purified human plasminogen but could not generate angiostatin in the absence of exogenous plasminogen. The fragmented proteins were reacted with the monoclonal antibody specific for plasminogen lysine-binding site 1 (LBS-1). Immunohistochemically, the intracytoplasmic immunostaining of LBS-1 was positive in 87.3% (48 of 55) of prostate carcinoma cases, and the immunostaining of miniplasminogen was negative in all cases. There was a significant relationship between the positive immunostaining of LBS-1 and Gleason score (P = 0.0007). The intracytoplasmic immunostaining of PSA was positive in 37.0% (20 of 54) of prostate carcinoma cases, but there was no significant relationship between the expression of PSA and Gleason score, or between the positive immunostaining of LBS-1 and PSA.
Conclusions:
These findings suggest that angiostatin is generated by prostate carcinoma cells and is accumulated within the cytoplasm. In addition, the generation of angiostatin-like fragments was correlated with tumor grade; however, PSA may not be the only enzyme for angiostatin generation in human prostate carcinoma.
Insights
Angiostatin, an inhibitor of tumor growth, is generated by prostate cancer cells and accumulates in the cytoplasm. Its generation correlates with tumor grade, but prostate-specific antigen (PSA) may not be the sole enzyme involved.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Angiostatin inhibits angiogenesis and tumor metastasis.
- Angiostatin is derived from plasminogen via proteolytic cleavage.
- The specific enzymes and localization of angiostatin in human tissues remain unclear.
Purpose of the Study:
- To investigate the generation and intracellular localization of angiostatin in prostate carcinoma.
- To identify potential enzymes involved in angiostatin generation within prostate cancer cells.
Main Methods:
- Analyzed angiostatin generation in human prostate cancer cell lines.
- Performed immunohistochemistry for angiostatin, plasminogen lysine-binding site 1 (LBS-1), miniplasminogen, and prostate-specific antigen (PSA) in 55 prostate carcinoma cases.
- Assessed the relationship between immunostaining results and Gleason score.
Main Results:
- Prostate carcinoma cell lysates generated angiostatin-like fragments from plasminogen.
- Intracytoplasmic LBS-1 immunostaining was positive in 87.3% of cases and correlated significantly with Gleason score (P = 0.0007).
- Prostate-specific antigen (PSA) expression was observed in 37.0% of cases, with no significant correlation to LBS-1 or Gleason score.
Conclusions:
- Prostate carcinoma cells generate and accumulate angiostatin within the cytoplasm.
- Angiostatin generation correlates with prostate cancer tumor grade.
- PSA is likely not the exclusive enzyme responsible for angiostatin generation in prostate carcinoma.
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