鼻咽癌组织中肿瘤干细胞的鉴别及其临床意义研究

目的鉴别鼻咽癌组织中肿瘤干细胞的存在以及探讨其临床意义。方法采用免疫组织化学方法对32例鼻咽癌组织（其中5例为高分化鳞癌、18例为中分化角化型鳞癌、9例为未分化型）的胚胎干细胞表面标志物SOX2和OCT4进行检测,并对鼻咽癌细胞的增殖能力以及Notchl信号途径的相关蛋白及其下游靶基因的蛋白表达进行检测。结果在所有3种类型的鼻咽癌组织中均发现有部分细胞表达胚胎干细胞的标记物SOX2和OCT4,其阳性率分别为65．6％（21／32）和71．9％（23／32）,而在正常的鼻咽部黏膜中则没有表达。在SOX2和OCT4阳性表达细胞中,中分化非角化型（49．3％）以及未分化型（51．5％）的增殖指数显著高于高分化角化型（31．2％）（P〈0．05）,并且Notchl受体（阳性率为78．1％,25／32）及其活化形式NICD（阳性率为68．8％,22／32）以及其下游靶基因HeM（阳性率为65．6％,21／32）在这些细胞中均有明显表达。结论在鼻咽癌组织中存在着肿瘤干细胞,并且Notchl信号途径在这些细胞中呈激活状态,肿瘤干细胞在鼻咽癌的发生、发展中可能具有重要意义。

Identification of cancer stem cells in nasopharyngeal carcinoma and its clinic significance

Objective To identify the cancer stem cells （CSCs） in nasopharyngeal carcinoma （NPC） and to in- vestigate its clinic significance. Methods Immunocytochemistry was performed to detect markers of embryonic stem （ES） cell proteins（SOX2 and OCT4）, proliferation of cancer cells and Notchl signaling components in 32 patients with NPC （5 cases of well-differentiated keratinizing type, 18 cases of moderately differentiated nonkeratinizing type, and 9 cases of undifferentiated type）. Results ES cell protein markers SOX2 （65.6%） and OCT4 （71.9%） were expressed in a subpopulation of cells of all three subtypes of NPC but not in the normal control. The proliferating index in moderate- ly differentiated nonkerationizing type（49.3% ） and undifferentiated type （51.5%） was significantly higher than in well- differentiated keratinizing type （31. 2% ）. Both Notch1 and NICD were expressed in SOX2- and OCT4-positive cells of NPC Hesl, a downstream target of Notchl signaling, was predominantly found in SOX2- and OCT4-positive cells. Con- clusions There were CSCs in NPC, and Notchl signaling pathway was activated in these cells. CSCs might play impor- tant roles in the malignancy of NPC.