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首页> 外文期刊>Cancer biology & therapy >The role of relaxin in endometrial cancer.
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The role of relaxin in endometrial cancer.

机译：松弛素在子宫内膜癌中的作用。

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Relaxin (RLN) is a naturally occurring hormone that is known to modulate connective tissue remodeling in the uterus and cervix. Our goal was to investigate the role of RLN in endometrial cancer. RLN expression was evaluated using immunohistochemistry in 57 samples of invasive endometrial carcinoma (EC) and ten benign endometrial tissues. 67% of high-stage (III/IV) tumors demonstrated strong RLN expression compared to 37% of low-stage (I/II) cases. Strong RLN expression associated significantly with high-grade and depth of myometrial invasion. Notably, strong RLN expression was associated with a significantly shorter overall survival (p < 0.005) compared to weak or moderate expression. Using RT-PCR, the expression of RLN and its receptor (LGR7) was detected in EC cell lines (HEC-1B and KLE); in addition, LGR7 was expressed in 86% of 15 primary EC tissue samples. Exogenous RLN stimulation caused a significant increase in migration and invasion in both cell lines, but did not stimulate proliferation in vitro. Addition of the MMP inhibitor, FN439 abolished the stimulatory effect of RLN on invasion in both HEC-1B and KLE cells. RLN stimulation caused a significant increase in levels of activated MMP-2 in KLE cells and activated MMP-9 in HEC-1B cells compared to unstimulated cells. Inhibition of endogenous RLN signaling via siRNA targeted to LGR7 caused a significant reduction of EC cell invasiveness. Our results indicate that RLN overexpression is significantly asso- ciated with aggressive features such as high-grade and deep myometrial invasion. We provide the first evidence that overexpression of RLN is associated with poor clinical outcome in women with EC. RLN stimulation enhances the invasive potential of endometrial cancer cells by upregulating MMPs. In turn, downregulation of endogenous RLN signaling decreases invasiveness of endometrial cancer cells. These novel findings may have therapeutic implications in the management of patients with endometrial carcinoma.
机译：松弛素（RLN）是一种天然激素，已知可调节子宫和子宫颈的结缔组织重塑。我们的目标是研究RLN在子宫内膜癌中的作用。使用免疫组化技术在57例浸润性子宫内膜癌（EC）和十个良性子宫内膜组织样品中评估RLN表达。 67％的高分期（III / IV）肿瘤表现出较强的RLN表达，而低位（I / II）则为37％。强烈的RLN表达与肌层高度和深度浸润显着相关。值得注意的是，与弱或中度表达相比，强RLN表达与总体生存期明显缩短（p <0.005）有关。使用RT-PCR，在EC细胞系（HEC-1B和KLE）中检测到了RLN及其受体（LGR7）的表达;此外，LGR7在15种原发性EC组织样品中的86％表达。外源性RLN刺激导致两种细胞系中迁移和侵袭的显着增加，但并未刺激体外增殖。加入MMP抑制剂FN439消除了RLN对HEC-1B和KLE细胞侵袭的刺激作用。与未刺激的细胞相比，RLN刺激导致KLE细胞中活化的MMP-2和HEC-1B细胞中活化的MMP-9水平显着增加。通过靶向LGR7的siRNA抑制内源性RLN信号传导，可显着降低EC细胞的侵袭性。我们的结果表明，RLN的过度表达与侵袭性特征（如高级别和深层肌层浸润）显着相关。我们提供的第一个证据表明，RLN的过度表达与EC妇女的临床预后不良有关。 RLN刺激通过上调MMPs来增强子宫内膜癌细胞的浸润潜能。反过来，内源性RLN信号的下调会降低子宫内膜癌细胞的侵袭性。这些新发现可能对子宫内膜癌患者的治疗具有治疗意义。

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