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Literature summary extracted from

  • Mattsson, J.M.; Laakkonen, P.; Stenman, U.H.; Koistinen, H.
    Antiangiogenic properties of prostate-specific antigen (PSA) (2009), Scand. J. Clin. Lab. Invest., 69, 447-451.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
3.4.21.77 additional information the prostate that produce several proteases can activate proPSA. A peptide that stimulates the activity of PSA enhaces the antiangiogenic effect Homo sapiens

Application

EC Number Application Comment Organism
3.4.21.77 medicine serum PSA is a very useful biomarker for prostate cancer. PSA at the same time stimulates tumor cell invasion and inhibits the formation of metastatic tumors by inhibiting angiogenesis. High PSA expression in the prostate is associated with low microvessel density, whereas low PSA expression is associated with poor prognosis. PSA is a potential target for prostate cancer treatment and imaging, it may be possible to control tumor angiogenesis and, thus, prostate cancer growth by modulating the proteolytic activity of PSA Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.21.77 alpha1-Aantichymotrypsin can block the PSA antiangiogenic effect Homo sapiens

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
3.4.21.77 28000
-
-
 Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
3.4.21.77 Homo sapiens
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.4.21.77 HUVEC cell
-
 Homo sapiens
-
3.4.21.77 LNCaP cell
-
 Homo sapiens
-
3.4.21.77 additional information different PSA isoforms in seminal fluid, which differ with respect to glycosylation and/or internal cleavages, and enzymatic activity Homo sapiens
-
3.4.21.77 prostate
-
 Homo sapiens
-
3.4.21.77 prostate cancer cell PC3 cell, elevated levels of PSA Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.21.77 plasminogen + H2O
-
 Homo sapiens angiostatin-like fragments
-
 ?
3.4.21.77 semenogelin + H2O
-
 Homo sapiens semenogelin fractions
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.4.21.77 kallikrein-related peptidase 3
-
 Homo sapiens
3.4.21.77 KLK3
-
 Homo sapiens
3.4.21.77 prostate-specific antigen
-
 Homo sapiens
3.4.21.77 PSA
-
 Homo sapiens

Expression

EC Number Organism Comment Expression
3.4.21.77 Homo sapiens PSA expression is lower in malignant than in normal prostatic epithelium and it is further reduced in poorly differentiated tumors down
3.4.21.77 Homo sapiens inactive proenzyme is produced at high concentrations by epithelial cells of the prostate up

General Information

EC Number General Information Comment Organism
3.4.21.77 malfunction recombinant mutant PSA, that lacks enzymatic activity towards a small chromogenic PSA substrate, also exerts antiangiogenic activity. HUVEC tube formation model shows that inactive PSA isoforms do not have antiangiogenic activity. Inhibition of PSA, either by a monoclonal antibody or small molecule inhibitors abolishes the effect of PSA Homo sapiens
3.4.21.77 physiological function active PSA exerts chymotrypsin-like enzymatic activity and efficiently digests semenogelins, which leads to liquefaction of the seminal clot. PSA inhibits angiogenesis both in in vitro and in vivo models. The antiangiogenic activity of PSA is related to its enzymatic activity and may be associated with the slow growth of prostate cancer. Purified PSA reduces the fibroblast growth factor 2-stimulated proliferation of HUVECs, bovine adrenal capillary endothelial cells and human microvascular dermal cells, while B16BL6 and human prostate cancer (PC3) cells are unaffected. Angiogenesis inducing cysteine-rich 61 is dramatically down-regulated by PSA in PC-3M and LNCaP prostate cancer cell lines. Inhibitory effect of enzymatically active PSA in seminal fluid is dose-dependent and significant inhibition is observed at a concentration of 0.0001 mM, which is over 10fold lower that found in the extracellular fluid in the prostate. Subcutaneously injected PSA reduces angiogenesis and xenograft tumor growth in mice and subcutaneously administered PSA reduces the metastatic propensity of intravenously injected melanoma cells Homo sapiens