摘要
胰腺癌是一种侵袭性恶性肿瘤,有很高的远处转移率、复发率及致死率。近年研究发现,肿瘤组织中的肿瘤干细胞(CSCs)在肿瘤的发生、发展、转移、复发以及耐药中起着重要作用。CSCs标记物对肿瘤临床诊断及预后分析有潜在价值,并可能是潜在的治疗靶点。胰腺癌预后不良可能由胰腺CSCs的存在引起的,因此,对胰腺CSCs的研究与鉴定将有助于胰腺癌发病机制的认识与新疗法的推出。
胰腺癌是最致命的癌症之一,发病隐匿,侵袭性强,预后
肿瘤干细胞(cancer stem cells,CSCs),也称为肿瘤起始细胞(tumor initiating cells,TICs)参与肿瘤起始、维持及稳定肿瘤异质性等过程,在肿瘤的发生、发展过程中发挥了关键作
胰腺CSCs可表达多种分子,包括CD44、CD24、CD133、上皮细胞黏附分子(Epithelial cell adhesion molecule,EpCAM)、细胞间质上皮转换因子(cellular-mesenchymal epithelial transition factor,c-Met)、醛脱氢酶1(aldehyde dehydrogenas 1,ALDH1)、C-X-C基序趋化因子受体4(C-X-C motif chemokine receptor 4,CXCR4)、腺苷三磷酸结合盒转运蛋白G2(ATP binding cassette subfamily G member 2,ABCG2)、双皮质激素样激酶1(doublecortin-like kinase 1,DCLK-1)、谷氧还蛋白3(glutaredoxin 3,GLRX3)、富含亮氨酸重复序列的G蛋白偶联受体5(eucine-rich-repeat-containing G-protein-coupled receptor 5,Lgr5)、Nanog、Oct4、Sox2、CD9、α6β4、巢蛋白(nestin)
CD44是透明质酸(hyaluronic acid)和骨桥蛋白(osteopontin)的跨膜糖蛋白和细胞表面黏附受体,是胰腺癌中重要的CSCs标记物之
CD133是一种糖基化的五跨蛋白,已作为胰腺癌的CSCs标记
CXCR4是一种G蛋白偶联趋化因子受体,在CSCs,尤其是迁移性CSCs中上调。在胰腺CSCs中,CD133和CXCR4的联合表达与侵袭和转移能力的增强相关,而这可通过阻断CXCR4预
c-Met是肝细胞生长因子(hepatocyte growth factor,HGF)的酪氨酸激酶受体,是胰腺CSCs的另一个标志记
ALDH1是酶的超家族成员之一,已用作胰腺癌实验研究中的CSCs标记
EpCAM虽然被视为CSCs标记物之一,但关于其与CSCs特异性是否相关的信息有
DCLK-1已被鉴定为胃肠道、胰腺和人类结肠癌细胞中的CSCs标记
CSCs通过过表达标记物,如Sox、Nanog、Oct4,增强自我更新特征和多能
CSCs是一种有前景的癌症治疗靶点,任何针对CSCs的治疗都具有改善癌症治疗和预后的巨大潜力。本文总结了几种当前已知的胰腺CSCs标记物在胰腺癌细胞的增殖、转移、侵袭、耐药及预后方面的作用。尽管CSCs标记物在肿瘤间或物种间的相对重叠较小,目前仍然无法确定哪些亚群细胞是CSCs,并且一些标记物的使用尚存在争议。随着研究的不断深入和技术的不断更新,越来越多的胰腺CSCs标记物将会被鉴定出来,对于胰腺CSCs在胰腺癌中的作用机制和相关信号通路的研究也日趋深入,胰腺CSCs标记物将在胰腺癌的早期诊断、靶向治疗及预后评估中发挥更重要的作用。
作者贡献声明
赵旭直接参与文献选题,负责文献资料解读分析和文章初稿撰写;闫思琦负责文献检索及内容审阅;赵建国负责文献总体选题和设计、文献稿件最终审阅定稿,对学术问题进行解答,并最终同意论文发表。
利益冲突
所有作者均声明不存在利益冲突。
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