Kiyohara M H, Dillard C, Tsui J, Kim S R, Lu J, Sachdev D, Goodglick L, Tong M, Torous V F, Aryasomayajula C, Wang W, Najafzadeh P, Gordon L K, Braun J, McDermott S, Wicha M S, Wadehra M
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Center to Eliminate Cancer Health Disparities, Charles Drew University, Los Angeles, CA, USA.
Oncogene. 2017 Oct 19;36(42):5793-5807. doi: 10.1038/onc.2017.142. Epub 2017 Jun 12.
Previous studies have suggested that overexpression of the oncogenic protein epithelial membrane protein-2 (EMP2) correlates with endometrial carcinoma progression and ultimately poor survival from disease. To understand the role of EMP2 in the etiology of disease, gene analysis was performed to show transcripts that are reciprocally regulated by EMP2 levels. In particular, EMP2 expression correlates with and helps regulate the expression of several cancer stem cell associated markers including aldehyde dehydrogenase 1 (ALDH1). ALDH expression significantly promotes tumor initiation and correlates with the levels of EMP2 expression in both patient samples and tumor cell lines. As therapy against cancer stem cells in endometrial cancer is lacking, the ability of anti-EMP2 IgG1 therapy to reduce primary and secondary tumor formation using xenograft HEC1A models was determined. Anti-EMP2 IgG1 reduced the expression and activity of ALDH and correspondingly reduced both primary and secondary tumor load. Our results collectively suggest that anti-EMP2 therapy may be a novel method of reducing endometrial cancer stem cells.
先前的研究表明，致癌蛋白上皮膜蛋白2（EMP2）的过表达与子宫内膜癌的进展相关，并最终导致患者预后不良。为了了解EMP2在疾病病因中的作用，我们进行了基因分析，以显示受EMP2水平反向调控的转录本。具体而言，EMP2的表达与几种癌症干细胞相关标志物的表达相关并有助于调节这些标志物的表达，其中包括醛脱氢酶1（ALDH1）。在患者样本和肿瘤细胞系中，ALDH的表达均显著促进肿瘤起始，并与EMP2的表达水平相关。由于缺乏针对子宫内膜癌中癌症干细胞的治疗方法，我们使用异种移植HEC1A模型确定了抗EMP2 IgG1疗法减少原发性和继发性肿瘤形成的能力。抗EMP2 IgG1降低了ALDH的表达和活性，并相应地降低了原发性和继发性肿瘤负荷。我们的研究结果共同表明，抗EMP2疗法可能是一种减少子宫内膜癌干细胞的新方法。
