Endometrial Stromal Cells Regulate Gap‐Junction Function in Normal Human Endometrial Epithelial Cells but not in Endometrial Carcinoma Cells

Endometrial Stromal Cells Regulate Gap‐Junction Function in Normal Human Endometrial Epithelial Cells but not in Endometrial Carcinoma Cells
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DOI:
10.1002/1098-2744(200006)28:2
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发表时间:
2000-06
影响因子:
4.6
通讯作者:
S. Schlemmer;D. Kaufman
S. Schlemmer;D. Kaufman
中科院分区:
医学2区
文献类型:
--
作者:
S. Schlemmer;D. Kaufman

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缝隙连接是由六个连接蛋白亚基组成的跨膜蛋白,通过缝隙连接促进相邻细胞之间的直接溶质运输。之前来自其他实验室的研究已经证明了缝隙连接功能降低与恶性转化之间的相关性。子宫内膜癌的一个典型表现是恶性上皮细胞周围的间质细胞数量减少。因此,本研究的重点是确定子宫内膜间质细胞对正常和恶性子宫内膜上皮细胞缝隙连接功能的影响。为了进行这些研究,我们评估了正常子宫内膜上皮细胞和人类子宫内膜上皮细胞,包括FEEC(用猴病毒40大T抗原永生化的胎儿子宫内膜上皮细胞)、HEC-1A(子宫内膜癌1A期)和RL-95-2(子宫内膜癌II级)。细胞间缝隙连接通讯(GJIC)在所有细胞系中均未显示。正常上皮细胞GJIC水平较低,而间质细胞间GJIC水平较高。当与基质细胞共培养时,上皮细胞间的GJIC水平升高。转化的上皮细胞单独培养或与基质细胞共培养时均未见GJIC。这些结果表明,子宫内膜间质细胞可能有助于调节子宫内膜上皮细胞的这种分化功能,而恶性子宫内膜上皮细胞对这些调节信号没有反应。摩尔。癌症。2000年,28:70-75。©2000 Wiley-Liss Inc.
Gap junctions are transmembrane proteins comprised of six connexin subunits that facilitate direct solute transport between adjacent cells through gap junctions. Previous studies from other laboratories have documented a correlation between reduced gap‐junction function and malignant transformation. In endometrial cancer, a characteristic finding is a reduction in the number of stromal cells surrounding the malignant epithelial cells. Thus, the focus of this study was to determine the effect of endometrial stromal cells on gap‐junction function in normal and malignant endometrial epithelial cells. To perform these studies, we evaluated normal endometrial epithelial cells and human endometrial epithelial cells including FEEC (fetal endometrial epithelial cells immortalized with simian virus 40 large‐T antigen), HEC‐1A (endometrial carcinoma stage 1A), and RL‐95‐2 (endometrial carcinoma grade II). Gap‐junctional intercellular communication (GJIC) could not be demonstrated for any of the cell lines. Low levels of GJIC were observed for normal epithelial cells and higher levels were found between stromal cells. Increased levels of GJIC were observed between the epithelial cells when they were cocultured with stromal cells. The transformed epithelial cells showed no GJIC when cultured alone or when in coculture with stromal cells. The results suggest that endometrial stromal cells may help to regulate this differentiated function of endometrial epithelial cells and that malignant endometrial epithelial cells are not responsive to these regulatory signals. Mol. Carcinog. 28:70–75, 2000. © 2000 Wiley‐Liss, Inc.