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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• 作者：Wen G. Jiang ; Richard J. Ablin ; Howard G. Kynaston ; Malcolm D. Mason
• 关键词：Endothelial cells ; Tumor-endothelial interaction ; Transglutaminase-4 ; Endothelial invasion ; Electric cell impedance sensing ; Prostate cancer ; Hepatocyte growth factor ; ROCK
• 刊名：Microvascular Research
• 出版年：2009
• 出版时间：March 2009
• 年：2009
• 卷：77
• 期：2
• 页码：150-157
• 全文大小：1019 K

文摘

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.