The accumulation of angiostatin-like fragments in human prostate carcinoma

Citation
T. Migita et al., The accumulation of angiostatin-like fragments in human prostate carcinoma, CLIN CANC R, 7(9), 2001, pp. 2750-2756
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
9
Year of publication
2001
Pages
2750 - 2756
Database
ISI
SICI code
1078-0432(200109)7:9<2750:TAOAFI>2.0.ZU;2-K
Abstract
Purpose: Angiostatin, a potent inhibitor of angiogenesis and, hence, the gr owth of tumor cell metastasis, is generated by a proteolytic enzyme from pl asminogen. However, its localization and specific enzymes have yet to be as certained in human tissue. Experimental Design: To elucidate the generation and the localization of an giostatin in prostate carcinoma, we examined angiostatin generation in a pa nel of human prostate cancer cell lines and performed immunohistochemistry with the antibodies to angiostatin and prostate-specific antigen (PSA), a p otent 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 plasmin ogen but could not generate angiostatin in the absence of exogenous plasmin ogen. The fragmented proteins were reacted with the monoclonal antibody spe cific 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 intra cytoplasmic immunostaining of PSA was positive in 37.0% (20 of 54) of prost ate 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 prosta te carcinoma cells and is accumulated within the cytoplasm. In addition, th e generation of angiostatin-like fragments was correlated with tumor grade; however, PSA may not be the only enzyme for angiostatin generation in huma n prostate carcinoma.