Department of Radiooncology and Radiotherapy, University Medical Center, Mainz, Germany.
Br J Cancer. 2013 Feb 5;108(2):402-8. doi: 10.1038/bjc.2012.570. Epub 2013 Jan 15.
Experimental studies have established a causal connection between tumour hypoxia, hypoxia-associated proteome changes and downregulation of E-cadherin, the final common pathway of epithelial-to-mesenchymal transition (EMT). Our study aimed at elucidating the interrelationship of these processes in cancers of the uterine cervix in vivo.
Tumour oxygenation was assessed in 48 squamous cell carcinomas (SCC) of the uterine cervix using polarographic needle electrodes. The expression pattern of E-cadherin was investigated by immunohistochemistry and western blotting, and was compared with that of the hypoxia-inducible proteins glucose transporter (GLUT)-1 and carbonic anhydrase (CA) IX in biopsy specimens of the oxygenation measurement tracks.
The majority of cervical cancers (52%) were E-cadherin positive, with a complete absence of the antigen in only 10% of the tumours. No correlation was found between the level of E-cadherin expression and the oxygenation status (mean pO(2), median pO(2) and hypoxic fractions). In patients showing partial expression of E-cadherin (38%), staining was not preferentially diminished in GLUT-1- or CA IX-positive areas, and loss of E-cadherin occurred independently of tumour cell scattering.
Our data provide no evidence in favour of a hypoxia-induced EMT as a mechanistic basis of cervical cancer invasiveness.
实验研究已经证实肿瘤缺氧、与缺氧相关的蛋白质组变化以及 E-钙黏蛋白（上皮-间质转化（EMT）的最终共同途径）下调之间存在因果关系。我们的研究旨在阐明这些过程在体内宫颈鳞癌中的相互关系。
使用极谱针电极评估 48 例宫颈鳞癌（SCC）的肿瘤氧合情况。通过免疫组织化学和蛋白质印迹法研究 E-钙黏蛋白的表达模式，并将其与氧合测量轨迹活检标本中缺氧诱导蛋白葡萄糖转运蛋白（GLUT）-1 和碳酸酐酶（CA）IX 的表达模式进行比较。
大多数宫颈癌（52%）为 E-钙黏蛋白阳性，仅有 10%的肿瘤完全缺乏该抗原。E-钙黏蛋白表达水平与氧合状态（平均 pO(2)、中位数 pO(2)和缺氧分数）之间没有相关性。在 E-钙黏蛋白部分表达的患者（38%）中，染色并没有优先减少 GLUT-1 或 CA IX 阳性区域，E-钙黏蛋白的丢失独立于肿瘤细胞分散。
我们的数据没有提供支持缺氧诱导的 EMT 作为宫颈癌侵袭性的机制基础的证据。
