The DSCs-Expressed CD82 Controls the Invasiveness of Trophoblast Cells via Integrinbeta1/MAPK/MAPK3/1 Signaling Pathway in Human First-Trimester Pregnancy1

Abstract

CD82 is recognized as a wide-spectrum tumor metastasis suppressor that inhibits cancer cell motility and invasiveness. At the human maternal-fetal interface, the decidua is believed to effectively limit the inappropriate invasion of trophoblasts. Here we have found the transcription and translation of CD82 in decidual stromal cells (DSCs), whereas trophoblast cells do not express CD82. The in-cell Western analysis reveals attenuation of CD82 translation in DSCs by human chorionic gonadotropin (hCG), but not by estrogen or progesterone. It is demonstrated that silencing of CD82 by RNA interference increases integrinbeta1, decreases TIMP1 expression in DSCs, and promotes the invasion of the first-trimester human trophoblasts in the coculture. Moreover, U0126, or anti-integrinbeta1 neutralizing antibody, reverses the decreased TIMP1 expression and the increased invasiveness of trophoblast cells, and the antibody also inhibits the MAPK3/1 phosphorylation induced by CD82 silence. After transfection with CD82, the invasive index of BeWo cells decreases significantly with TIMP1 increase. The results above indicate that the DSCs-expressed CD82 up-regulates the expression of TIMP1 in an autocrine manner and inhibits the invasiveness of human first-trimester trophoblast cells partly through the integrinbeta1/MAPK/MAPK3/1 signaling pathway. Furthermore, we have found that the mRNA and protein level of CD82 in decidua of the miscarriage is significantly higher than that of the normal early pregnancy, which implies that the abnormal higher CD82 expression in decidua restricts appropriate invasion of trophoblasts that leads to early pregnancy wastage.

CD82 gene suppression in endometrial stromal cells leads to increase of the cell invasiveness in the endometriotic milieu

“…The expression of CD82 is involved in decidual transformation from human endometrial stromal cells (ESCs; Gellersen et al 2007). Moreover, our previous work has confirmed that CD82 in decidual stromal cells controls the trophoblasts invasiveness by suppressing integrinb1/mitogen-activated protein kinase (MAPK)/ ERK1/2 signal pathway in human early pregnancy (Li et al 2010). Interestingly, the decidualized ESCs support trophoblasts invasion by paracrine signals, such as HB-EGF, IL1, and LIF, which also can induce CD82 in ESCs for controlling trophoblasts invasion (Gonzalez et al 2011).…”

“…Moreover, the expression of integrins was intimately associated with the function of CD82. Our previous work has confirmed that DSCs-expressed CD82 controls the invasiveness of trophoblasts through suppressing the integrinb1/MAPK/ERK1/2 signal pathway (Li et al 2010). Therefore, we next investigated the protein levels of the invasion-relative molecules and integrins in the CD82-silenced ESCs from patients without endometriosis (nZ6).…”

Chemokine CCL24 promotes the growth and invasiveness of trophoblasts through ERK1/2 and PI3K signaling pathways in human early pregnancy

“…For primary culture, sterile villi (nZ242, age: 26G2.01 years, gestational age: 8G0.49) or deciduas (nZ26, age: 24G 3.75 years, gestational age: 7G1.53) samples were immediately put into ice-cold high D-glucose DMEM (HG-DMEM; Gibco Grand Island, NY, NY, USA), with 1% penicillin and streptomycin in the medium. Tissues were transported to the laboratory within 30 min, and then trophoblasts and DSCs were isolated according to our previous procedures (Li et al 2010). These methods supplied about 85% cytokeratin-positive purified trophoblasts, and about 98% vimentin-positive and cytokeratinnegative DSCs.…”

“…Cytokeratin 7 (CK7) is a protein that specifically expressed in epithelial tissues, and is used as a maker of trophoblast in villi (Li et al 2010). Freshly isolated trophoblasts were gently washed with PBS, and then mixed with mouse anti-human CK7-FITC MAB (BD, Franklin Lakes, NJ, USA) and CCR3-APC MAB (Biolegend, San Diego, CA, USA).…”

Stromal cells–are they really useful for GVHD?

“…In the BM, mesenchymal stromal cells (BM-MSCs) support hematopoietic cell development, 1 whereas decidual stromal cells (DSCs) in the placenta promote trophoblast invasion and therefore implantation of the developing fetus. 2 DSCs are also important for the development of feto-maternal tolerance. 3,4 Stromal cells have immunosuppressive capacity, [5][6][7] which paved the way for using them in the treatment of inflammatory diseases.…”