Isolation of a prostate carcinoma cell proliferation-inhibiting factor from human seminal plasma and its similarity to transforming growth factor beta.
Human seminal plasma (SP) has been known to contain both growth-inhibitory and -stimulatory factors. We attempted to identify a factor that inhibited DNA synthesis in some metastatic prostate cancer cell lines. The SP factor was sensitive to digestion by trypsin, but its activity increased after boiling or dialysis against 1 M acetic acid, by 3- to 4-fold. The SP factor was partially purified using a cation-exchange resin. Apparent molecular mass determination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed it to be a M(r) 25,000 protein, and M(r) 13,000 after reduction. This protein strongly inhibited DNA synthesis in two metastatic androgen-independent human prostatic carcinoma cell lines (PC3 and DU145) and the Dunning R3327G rat prostatic adenocarcinoma. It was ineffective on androgen-dependent LNCaP cells. The proliferation-inhibiting activity of this SP protein was specifically and completely abolished by a neutralizing anti-transforming growth factor beta (TGF-beta) antiserum. Furthermore, immunoblot analysis using the anti-TGF-beta antiserum showed the similarity of this protein to TGF-beta. The maximum concentration of this protein in SP was 165 +/- 11.7 ng/ml (mean +/- SD), of which only one-fourth may be present in active form under normal conditions. Identification of a TGF-beta-like protein in SP might also explain the variety of growth and immune modulation properties of human SP.
Lokeshwar
B L
BL
Department of Urology, University of Miami School of Medicine, Florida 33101.
Block
N L
NL
D000328:Adult; D000818:Animals; D006131:Growth Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D008297:Male; D008907:Mink; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000502:physiology; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D012661:Semen / Q000737:chemistry* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta