title: The prostate transglutaminase (TGase-4, TGaseP) regulates the interaction of prostate cancer and vascular endothelial cells, a potential role for the ROCK pathway.
abstract: 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.
authors.affiliation: Metastasis & Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. jiangw@cf.ac.uk
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Ablin
authors.forename: Howard G
authors.initials: HG
authors.lastname: Kynaston
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
mesh_terms: D001483:Base Sequence; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology*; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D016337:RNA, Catalytic; C427204:hammerhead ribozyme; C418702:transglutaminase 4; D011503:Transglutaminases; D054460:rho-Associated Kinases