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Recombinant human uteroglobin suppresses cellular invasiveness via a novel class of high-affinity cell surface binding site.

机译:重组人子宫珠蛋白通过一类新型的高亲和力细胞表面结合位点抑制细胞侵袭性。

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摘要

The mechanism(s) that regulates invasion of trophoblasts through the uterine epithelium during embryo implantation and nidation in hemochorial placental mammals is poorly understood. While limited trophoblast invasion is essential for the establishment of normal pregnancy, dysregulation of this process may contribute to the pathogenesis of choriocarcinoma, a highly invasive and lethal form of cancer arising from the trophoblasts. We have previously demonstrated that rabbit uteroglobin (UG), a cytokine-like, antiinflammatory protein, produced by the endometrial epithelium during pregnancy, has a potent antichemotactic effect on neutrophils and monocytes in vitro. Here, we report that recombinant human UG (hUG) dramatically suppresses invasion of human trophoblasts and NIH 3T3 cells through an artificial basement membrane (Matrigel) in vitro but has no effect on that of human choriocarcinoma cells. We identified a previously unreported high-affinity, high molecular weight (approximately 190 kDa), nonglycosylated hUG-binding protein, readily detectable on human trophoblasts and NIH 3T3 cells but totally lacking on choriocarcinoma cells. Taken together, these results raise the possibility that (i) hUG plays a critical role in regulating cellular invasiveness, at least in part, via its previously unrecognized cell surface binding site, and (ii) some of the numerous biological activities of proteins of the UG family, reported so far, may be mediated via this binding site.
机译:人们对在血chorchal胎盘哺乳动物的胚胎植入和消除过程中调节滋养层细胞通过子宫上皮细胞入侵的机制了解甚少。尽管有限的滋养细胞侵袭对正常怀孕的建立至关重要,但该过程的失调可能导致绒毛膜癌的发病机理,绒毛膜滋养细胞是高度侵袭性和致死性癌症。我们以前已经证明,兔子宫内珠蛋白(UG)是一种在怀孕期间子宫内膜上皮产生的细胞因子样抗炎蛋白,在体外对中性粒细胞和单核细胞具有有效的抗化学趋化作用。在这里,我们报道了重组人UG(hUG)可以在体外通过人工基底膜(Matrigel)显着抑制人滋养细胞和NIH 3T3细胞的侵袭,但对人绒癌组织没有影响。我们确定了以前未报道的高亲和力,高分子量(约190 kDa),非糖基化的hUG结合蛋白,在人滋养细胞和NIH 3T3细胞上很容易检测到,而绒癌组织则完全缺乏。综上所述,这些结果提高了以下可能性:(i)hUG至少部分地通过其先前无法识别的细胞表面结合位点在调节细胞侵袭性中起关键作用,以及(ii)蛋白质的许多生物学活性中的一些迄今为止报道的UG家族可以通过该结合位点介导。

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