title: Evidence that the prostate-specific antigen (PSA)/Zn2+ axis may play a role in human prostate cancer cell invasion.
abstract: Prostate-specific antigen (PSA), which is used as a marker for the diagnosis and monitoring of prostate cancer, is a kallikrein protease which could potentially play a role in human prostate cancer cell invasion. Zinc ions are effective inhibitors of a number of proteases. The enzymatic activity of purified PSA was strongly inhibited by Zn(2+). The ability of LNCaP cells which express and secrete PSA to invade Matrigel was strongly suppressed by Zn(2+) at a concentration similar to that inhibiting the activity of purified PSA. Zn(2+) effectively inhibited the degradation of Matrigel by purified PSA. These results suggest that Zn(2+) in human prostate may suppress the invasion and metastasis of prostate cancer cells through the regulation of the proteolytic activity of PSA. Loss of inhibition of the proteolytic activity of PSA by Zn(2+) in prostate tumors could contribute to invasion.
authors.affiliation: Laboratory of Pharmaceutics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Ishii
authors.forename: Takashi
authors.initials: T
authors.lastname: Otsuka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iguchi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Usui
authors.forename: Hajime
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sugimura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Simon W
authors.initials: SW
authors.lastname: Hayward
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirano
mesh_terms: D015153:Blotting, Western; D002412:Cations; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D007477:Ions; D007797:Laminin / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020842:Plasma Kallikrein / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011509:Proteoglycans / Q000737:chemistry / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002412:Cations; D004338:Drug Combinations; D007477:Ions; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D020842:Plasma Kallikrein; D017430:Prostate-Specific Antigen; D015032:Zinc