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.