Over‐expression of stomatin causes syncytium formation in nonfusogenic JEG‐3 choriocarcinoma placental cells

Abstract

Placental trophoblast differentiation involves the continuous fusion of mononuclear cytotrophoblasts. However, except for syncytin, little is known about the detailed mechanisms underlying trophoblast fusion. A previous study indicated that lipid rafts play an important role in HTLV-1 syncytium formation. To identify proteins that may be involved in placental trophoblast differentiation, we examined stomatin, an important lipid-raft protein that localizes to detergent-resistant membrane domains. The syncytium and human chorionic gonadotropin (β-hCG; a marker of placental trophoblast differentiation) were visualized by immunofluorescence staining. We found that overexpression of stomatin in the nonfusogenic JEG-3 cell line caused syncytium formation and increased the fusion index of cells. Treating these cells with N(6) ,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate further increased cell fusion by stomatin. β-hCG was found in a few JEG-3 cells overexpressing stomatin at 48 h, and its levels increased dramatically at 72 h along with the formation of the multinuclear syncytium. RNA interference was used to decrease stomatin expression in BeWo cells, a fusogenic human choriocarcinoma cell line. After knockdown for 72 h, stomatin levels decreased by almost 95%. The fusion indexes of control and stomatin-knockdown cells at 72 h were 9.4 and 6.5%, respectively. Our data indicated that stomatin could trigger syncytium formation and upregulate β-hCG for cell fusion in nonfusogenic JEG-3 cells. Downregulation of stomatin slightly inhibited the fusion index of fusogenic BeWo cells. Thus, these data suggested that stomatin plays an important role in trophoblast differentiation.

Structure-function analysis of human stomatin: A mutation study

“…Similarly, in neutrophils, stomatin is associated with azurophil granules, but also other specific granules [13], and is likewise relocated to the plasma membrane upon activation [1]. Stomatin is also expressed in placental cells, where it may play an important role in trophoblast differentiation [14], and in bone, where it promotes osteoclastogenesis [15]. Trafficking of stomatin to the plasma membrane appears to follow the Golgi-pathway [16], while endocytosis most probably follows a clathrin-independent endocytosis pathway similar to caveolin-1 [17] and flotillins [18].…”

<p>Silencing stomatin-like protein 2 attenuates tumor progression and inflammatory response through repressing CD14 in liver cancer</p>

“…19 Studies found that stomatin and its family members participate in the occurrence of malignant tumors, and that SLP-2 is overexpressed in choriocarcinoma placental cells, ovarian cancer, and cervical cancer; however, research on SLP-2 in liver cancer is rarely conducted. [20][21][22] We found for the first time that inhibiting the expression of SLP-2 gene in liver cancer cells could inhibit NF-kB, reduce the inflammatory response, and downregulate the expression levels of MMP-2 and MMP-9 and therefore inhibit the migration and invasion of liver cancer cells. 23 The purpose of this study was to investigate the effect of SLP-2 on liver cancer cells, and the data showed that the expression level of SLP-2 gene in liver cancer cells was higher than that in human normal liver cells, suggesting that SLP-2 is possibly involved in the growth of hepatoma cells.…”

The Candida albicans stress response gene Stomatin-Like Protein 3 is implicated in ROS-induced apoptotic-like death of yeast phase cells

“…Novel functional roles of stomatins have been implicated in over-expression analysis. In humans, over-expression of STOM and SLP-1 implicated roles in placental trophoblast differentiation and protein trafficking, respectively [ 31 , 48 ]. Also, SLP-2 over-expression was associated with several clinicopathological features in thyroid cancer patients [ 49 ].…”