Developmental Regulation of Tissue Transglutaminase During Human Placentation and Expression in Neoplastic Trophoblast

Abstract

The expression of tissue transglutaminase (tTG) was studied during the formation of the normal human placenta and in molar pregnancies and choriocarcinoma, in order to correlate its expression with the functional characteristics of the recognized trophoblast cell types. tTG expression was found to be developmentally regulated. Before 6–7 weeks' gestation, only the chorionic villous cytotrophoblast expresses tTG. Thereafter the overlying syncytiotrophoblast becomes positive. tTG expression is gradually downregulated in the intermediate trophoblast cells emerging from the tips of the chorionic villi invading the uterine tissue. In the decidual wall, the intermediate trophoblast does not express tTG, whereas scattered syncytial cells, the placental bed giant cells, express tTG. Villi from complete hydatidiform mole (CHM) show tTG expression in both the cyto‐ and the syncytiotrophoblast. The intermediate trophoblast cells from CHM show heterogeneous tTG expression, with a majority of negative cells, whereas extravillous syncytia always express tTG. In choriocarcinoma, the tumour cells show heterogeneous tTG expression, with a majority of positive cells. Analysis of tTG protein and mRNA in placental extracts by Western and Northern blotting did not provide evidence for expression of the truncated form of tTG found in some cell types. The regulated expression of tTG in the normal placenta suggests that the enzyme is involved in important trophoblastic functions and may participate in the control of invasion. © 1997 by John Wiley & Sons, Ltd.

Transglutaminase 2-dependent Deamidation of Glyceraldehyde-3-phosphate Dehydrogenase Promotes Trophoblastic Cell Fusion

“…29). In the human placenta, strong activity was identified at the syncytial microvillous membrane (30), where TG2 is seen in both syncytio-and cytotrophoblasts in association with the cytoskeletal structure, including peripheral actin bundles and stress fibers (19). Furthermore, TG2 might mediate polymerization of cytoskeletal proteins by crosslinking with, and thereby stabilizing, particle materials shed from placental villi (19).…”

Effect of single post-ovulatory administration of levonorgestrel on gene expression profile during the receptive period of the human endometrium

“…TGM2 plays an important role in the adhesion and migration of many cell types (Mohan et al 2003), including the trans-endothelial migration of blood cells, which may mimic the initial step in trophoblast invasion (Fazleabas et al 2004). While it has been observed that progesterone increases TGM2 transcript expression in Ishikawa endometrial cells (Li et al 2006), the activity of this enzyme is ten times higher in the secretory endometrium than the proliferative endometrium (Hager et al 1997). TGM2 mRNA also increases during the period of receptivity (Riesewijk et al 2003), suggesting that progesterone regulates the expression of TGM2 in vivo.…”

Expression of tissue transglutaminase in human bladder carcinoma

“…The tTG monoclonal antibody CUB74, raised against guinea pig liver TG, was used to visualize tTG as described previously 12 and the specificity was validated using Western blotting (cf. Fig.…”

“…11 We have recently shown that tTG is similarly down-regulated in the normal intermediate trophoblast, whereas dysregulation was found in choriocarcinoma cells. 12 The 6 4 integrin, which is normally located on the basal surface of the urothelial cell in close juxtaposition to collagen VII, is frequently either lost or deranged in invasive bladder cancer. 13 In addition, loss of membranous E-cadherin is associated with advanced tumour stage in bladder cancer, and with poor patient survival.…”