Enhanced progression of human prostate cancer PC3 cells induced by the microenvironment of the seminal vesicle.
The objective of this study was to characterise the mechanism mediating the prostate cancer progression induced by the microenvironment of seminal vesicle (SV). The invasive potential of PC3 cells significantly increased after treatment with extract from SV of NOD/SCID mouse. Among several growth factors and cytokines that were present in the SV extract, transforming growth factor-beta(1) (TGF-beta(1)) significantly enhanced the invasive potential of PC3 cells; however, the additional treatment with neutralising antibody against TGF-beta(1) suppressed the enhanced invasive potential induced by the SV extract. Changes in the invasive potential in PC3 cells after treatment with the SV extract and/or TGF-beta(1) were in proportion to those in the production of urokinase-type plasminogen activator (uPA) by PC3 cells. Tumour growth as well as the incidence of lymph node metastasis in NOD/SCID mice after the injection of PC3 cells into the SV were significantly greater than those after the injection into the prostate. These findings suggest that the microenvironment of SV enhances the progression of prostate cancer through a stimulated invasive potential, and that enhanced uPA production in prostate cancer cells induced by TGF-beta(1) could therefore be one of the most important mechanisms involved in the progression of prostate cancer after SV invasion.
Kumano
M
M
Department of Surgery, Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Miyake
H
H
Kurahashi
T
T
Yamanaka
K
K
Fujisawa
M
M
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D018450:Disease Progression; D045604:Extracellular Fluid / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012669:Seminal Vesicles / Q000473:pathology / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D053773:Transforming Growth Factor beta1; D014568:Urokinase-Type Plasminogen Activator