The prostate transglutaminase (TGase-4, TGaseP) regulates the interaction of prostate cancer and vascular endothelial cells, a potential role for the ROCK pathway

The prostate transglutaminase (TGase-4, TGaseP) regulates the interaction of prostate cancer and vascular endothelial cells, a potential role for the ROCK pathway
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DOI:
10.1016/j.mvr.2008.09.010
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发表时间:
2009-03-01
影响因子:
3.1
通讯作者:
Mason, Malcolm D.
Mason, Malcolm D.
中科院分区:
医学3区
文献类型:
--
作者:
Jiang, Wen G.;Ablin, Richard J.;Mason, Malcolm D.

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前列腺转氨酶(TGase-4或TGaseP)是一种在前列腺组织中独特表达的酶。涉及细胞基质的TGase的功能尚未完全确定。在本研究中,我们研究了TGase-4在肿瘤-内皮细胞相互作用中的作用,通过创建一组具有不同表达谱的人TGase-4的前列腺癌细胞系。在这里,我们报告说,前列腺癌细胞PC-3,当过表达TGase-4(PC-3(TGase 4 exp))增加他们的能力,坚持静止和激活(肝细胞生长因子)内皮细胞。相反,表达高水平TGase-4的前列腺癌细胞CAHPV-10在TGase-4表达被敲低后减少了对内皮细胞的粘附。通过使用基于频率的电细胞阻抗感测,我们发现TGase-4介导的粘附导致低频(400 Hz)下的阻抗变化,表明细胞旁通路中断。该研究进一步表明,TGase-4的表达使得细胞通过绕过ROCK途径来发挥对内皮相互作用的调节。因此得出结论,TGase-4在内皮细胞和前列腺癌细胞之间的相互作用中起关键作用,该作用独立于ROCK途径。(c)2008年爱思唯尔公司All rights reserved.
Prostate transglutaminase (TGase-4 or TGaseP) is an enzyme that is uniquely expressed in prostate tissues. The function of the TGase, implicated in the cell-matrix, is yet to be fully established. In the present study, we investigated the role of TGase-4 in tumor-endothelial cell interactions, by creating a panel of prostate cancer cell lines that have different expression profiles of human TGase-4. Here, we report that prostate cancer cells PC-3, when over-expressing TGase-4 (PC-3(TGase4exp)) increased their ability to adhere to quiescent and activated (by hepatocyte growth factor) endothelial cells. in contrast, the prostate cancer cell CAHPV-10, which expressed high levels of TGase-4, reduced the adhesiveness to the endothelial cells after TGase-4 expression was knocked down. By using frequency based electric cell impedance sensing, we found that TGase-4 mediated adhesion resulted in a change in impedance at low frequency (400 Hz), indicating a paracellular pathway disruption. The study further showed that expression of TGase-4 rendered the cells to exert regulation of endothelial interaction by bypassing the ROCK pathway. It is therefore concluded, that TGase-4 plays a pivotal role in the interaction between endothelial cells and prostate cancer cells, an action which is independent of the ROCK pathway. (c) 2008 Elsevier Inc. All rights reserved.