Enhanced progression of human prostate cancer PC3 cells induced by the microenvironment of the seminal vesicle
Enhanced progression of human prostate cancer PC3 cells induced by the microenvironment of the seminal vesicle
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DOI：
10.1038/sj.bjc.6604169
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发表时间：
2008-01-22
影响因子：
8.8
通讯作者：
Fujisawa, M.
中科院分区：
文献类型：
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作者：
Kumano, M.;Miyake, H.;Fujisawa, M.
本研究的目的是表征精囊微环境（SV）诱导前列腺癌进展的机制。经NOD/SCID小鼠SV提取物处理后，PC3细胞的侵袭潜能显著增加。在SV提取物中存在的几种生长因子和细胞因子中，转化生长因子- β (1) （tgf - β(1)）显著增强了PC3细胞的侵袭潜能；然而，用抗tgf - β(1)的中和抗体进行额外处理抑制了SV提取物诱导的增强侵袭电位。经SV提取物和/或tgf - β(1)处理后，PC3细胞侵袭电位的变化与PC3细胞产生尿激酶型纤溶酶原激活剂（uPA）的变化成正比。PC3细胞注射到SV后，NOD/SCID小鼠的肿瘤生长和淋巴结转移发生率明显高于注射到前列腺后。这些发现表明，SV微环境通过刺激侵袭电位促进前列腺癌的进展，tgf - β诱导前列腺癌细胞中uPA生成的增强(1)可能是SV侵袭后前列腺癌进展的最重要机制之一。
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.