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

• Published in: Microvascular research 2009-03, Vol.77 (2), p.150-157
• Main Authors: Jiang, Wen G., Ablin, Richard J., Kynaston, Howard G., Mason, Malcolm D.
• Format: Article
• Language: English
• Subjects: Base Sequence; Cell Adhesion; Cell Communication; Cell Line; Cell Line, Tumor; DNA Primers - genetics; Electric cell impedance sensing; Endothelial cells; Endothelial Cells - enzymology; Endothelial Cells - pathology; Endothelial invasion; Gene Expression; Hepatocyte growth factor; Humans; Male; Neoplasm Invasiveness; Prostate cancer; Prostatic Neoplasms - blood supply; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - pathology; rho-Associated Kinases - metabolism; RNA, Catalytic - genetics; RNA, Catalytic - metabolism; ROCK; Transglutaminase-4; Transglutaminases - antagonists & inhibitors; Transglutaminases - genetics; Transglutaminases - metabolism; Tumor-endothelial interaction
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1016/j.mvr.2008.09.010

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.