An amino-terminal fragment of urokinase isolated from a prostate cancer cell line (PC-3) is mitogenic for osteoblast-like cells.
A peptide mitogen for cultured osteoblast-like cells was purified from serum-free conditioned culture medium of a human prostatic cancer cell line, PC-3. Based on amino acid sequencing and estimated molecular weight, this peptide was identified as an NH2-terminal fragment of urokinase-type plasminogen activator (uPA). Recombinant high molecular weight (HMW) uPA and the NH2-terminal growth factor domain (GFD) of uPA, but not low molecular weight (LMW) uPA (lacking the NH2-terminal region) stimulated [3H] thymidine incorporation and proliferation in osteoblast-like cells, and specific, competitive binding sites for HMW, but not LMW, uPA were demonstrable. These studies demonstrate the production of a mitogenic NH2-terminal fragment of uPA by a human prostatic cancer cell line which may be of importance in the pathogenesis of osteoblastic metastases.
Rabbani
S A
SA
Department of Physiology, McGill University, Montreal, Quebec, Canada.
Desjardins
J
J
Bell
A W
AW
Banville
D
D
Mazar
A
A
Henkin
J
J
Goltzman
D
D
D000230:Adenocarcinoma / Q000201:enzymology* / Q000556:secondary; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001859:Bone Neoplasms / Q000201:enzymology* / Q000556:secondary; D002471:Cell Transformation, Neoplastic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology*; D012516:Osteosarcoma / Q000201:enzymology* / Q000556:secondary; D010960:Plasminogen Activators / Q000302:isolation & purification*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000556:secondary; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000302:isolation & purification*
D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator