key: cord-0845136-91cx2jye authors: nan title: CD133作为肺癌干细胞标记物的应用及其局限性 date: 2011-10-20 journal: Zhongguo Fei Ai Za Zhi DOI: 10.3779/j.issn.1009-3419.2011.10.10 sha: dd63f666cdfaa58b86aa76662671a3d880892f59 doc_id: 845136 cord_uid: 91cx2jye Lung cancer is one of the most common tumor, which lacks of effective clinical treatment to lead to desirable prognosis. According to cancer stem cell hypothesis, lung cancer stem cells are considered to be responsible for carcinogenesis, development, metastasis, recurrence, invasion, resistance to chemotherapy and radiotherapy of lung cancer. In recent years, more and more institutes used glycosylated CD133 epitopes to define, isolate, purify lung cancer stem cells. However, along with deeply research, the application of CD133 epitopes in lung cancer stem cell research is questioned. The utilization and limitation of CD133 epitopes in lung cancer stem cells research for the past few years is summaried in this review. and limitation of CD133 epitopes in lung cancer stem cells research for the past few years is summaried in this review. 【Key words】 Stem cells; Lung neoplasms; CD133 、Notch、Shh (Sonichedgehog)和Bmi-1 等信号通路 [11] ， 它们的异常表达可引起细胞过度增殖而 导致肿瘤发生；③具有端粒酶活性以及扩增的端粒重复 序列，而人类终末分化体细胞不具有或者具有极低的端 粒酶活性 [12] ；④具有比较类似的表面标志物，如lnestin、 人CD133蛋白与鼠prominin-1(一种富集于神经上皮 干细胞顶端表面微绒毛上的表面蛋白)有大约60%的同源 性 [13] ， 故也称人CD133为人prominin-1。CD133是一个5次跨 膜糖蛋白，最初于1997年作为CD34阳性造血干细胞上的 表面抗原被AC133单抗靶定而被发现 [14] 。与此同时测定其 分子量约为97 kDa， 由865个氨基酸组成 [15] ， 包括85个氨基 胞内尾端。有研究 [14] 表明AC133抗原是一个表观分子量为 120 kDa的糖基化蛋白。同年发现了另一个CD133糖基化表 位-AC141 [15] 。荧光激活细胞分选术(f luorescence-activated cell sorting, FACS)显示抗AC133抗体和抗AC141抗体能够 识别空间结构特异的表位 [14] 。对经过衣霉素处理的细胞 进行免疫沉淀试验发现AC133和AC141都能够识别糖基化 的结构 [15] ，提示由抗AC141抗体所识别的CD133的糖基化 表位与抗AC133抗体所识别的CD133的糖基化表位空间结 构不一致， 分别称为AC133表位和AC141表位。 针对AC133 Ber tol i n i等 [ Cancer stem cell biology: from leukemia to solid tumors Organ-and tissue-specific stem cells and carcinogenesis Prominin, a novel microvillispecific polytypic membrane protein of the apical surface of epithelial cells AC133, a novel marker for human hematopoietic stem and progenitor cells A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning Identification and expansion of the tumorigenic lung cancer stem cell population Identification and expansion of human colon-cancer-initiating cells Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo Signalling, cell cycle and pluripotency in embryonic stem cells A multidrug resistance transporter from human MCF-7 breast cancer cells Prognostic value of CD133 expression in stage I lung adenocarcinomas CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for sur vival of non-small cell lung cancer patients Targeting CD133 antigen in cancer The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer Alternative promoters regulate transcription of the gene that encodes stem cell surface protein AC133 AC133-2, a novel isoform of human AC133 stem cell antigen Identification of novel prominin-1/CD133 splice variants with alternative C-termini and their expression in epididymis and testis Monoclonal antibody CD133-2(AC141) against hematopoietic stem cell antigen CD133 shows crossreactivity with cytokeratin 18 Prominin: a story of cholesterol, plasma membrane protrusions and human pathology New insights into the cell biology of hematopoietic progenitors by studying prominin-1 (CD133). Cells Tissues Organs A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas CD133 negative cancer stem cells in glioblastoma CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells et al． Glioblastoma-derived stem cel1-enriched cultures form distinct subgroups according to molecular and phenotypic criteria Isolation and identification of human lung adenocarcinoma stem cells. Tumor Both CD133+ and CD133-subpopulations of A549 and H446 cells contain cancer-initiating cells Hypoxia induces yumor aggressiveness and the expansion of CD133-positive cells in a hypoxia-inducible factor-1α-dependent manner in pancreatic cancer cells Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors Cancer stem cells as mediators of treatment resistance in brain tumors: status and controversies Limits of CD133 as a marker of glioma serf-renewing cells