RADIATION RESPONSE OF CANCER STEM-LIKE CELLS FROM ESTABLISHED HUMAN CELL LINES AFTER SORTING FOR SURFACE MARKERS
RADIATION RESPONSE OF CANCER STEM-LIKE CELLS FROM ESTABLISHED HUMAN CELL LINES AFTER SORTING FOR SURFACE MARKERS
复制标题
DOI：
10.1016/j.ijrobp.2009.07.001
复制
发表时间：
2009-11-15
影响因子：
7
通讯作者：
Brunner, Thomas B.
中科院分区：
文献类型：
--
作者：
Al-Assar, Osama;Muschel, Ruth J.;Brunner, Thomas B.
目的：假设肿瘤干细胞样细胞（cancer stem-like cells， CSLC）亚群存在于不同的癌细胞系中，并介导实体瘤的放射耐药。方法和材料：对细胞进行CSLC标记染色和分选（荧光活化细胞分选器/磁珠），比较不同器官的8种细胞系中已分选和未分选群体中磷酸化组蛋白H2AX Ser 139 （γ -H2AX）的病灶和放射敏感性。通过非锚定生长和激活Notch1水平来检测CSLC的特性。验证包括在异种移植物肿瘤中检测CSLC的致瘤性和放射后富集。结果：CSLC的数量与原发肿瘤基本一致。MDA-MB-231（乳腺）和Panc-1和PSN-1（胰腺）细胞的CSLC比未分选细胞的残余γ - h2ax灶少，表明CSLC具有放射抗性。然而，只有MDA-MB-231 CSLC比未分选的细胞更耐辐射。此外，MDA-MB-231 CSLC表现出增强的非锚定生长和激活的Notch1蛋白的过表达。分次辐射暴露后，MDA-MB-231异种移植瘤模型中肿瘤干细胞表面标记物的表达增加。与PSN-1细胞相比，发现MDA-MB-231 CSLC异种移植肿瘤与未分选细胞产生的肿瘤相比具有生长优势。结论：尽管在其他报告中显示CSLC亚群的数量相对较好地对应，但CSLC亚群没有普遍的放射抗性表型。同样，在一些但不是所有的测试细胞系中发现了CSLC特征。在细胞系中检测CSLC所报告的问题可以通过其他技术来克服，而不仅仅是对标记物进行分选。(C) 2009爱思唯尔公司
Purpose: A subpopulation of cancer stem-like cells (CSLC) is hypothesized to exist in different cancer cell lines and to mediate radioresistance in solid tumors.Methods and Materials: Cells were stained for CSLC markers and sorted (fluorescence-activated cell sorter/magnetic beads) to compare foci and radiosensitivity of phosphorylated histone H2AX at Ser 139 (gamma-H2AX) in sorted vs. unsorted populations in eight cell lines from different organs. CSLC properties were examined using anchorage-independent growth and levels of activated Notch1. Validation consisted of testing tumorigenicity and postirradiation enrichment of CSLC in xenograft tumors.Results: The quantity of CSLC was generally in good agreement with primary tumors. CSLC from MDA-MB-231 (breast) and Panc-1 and PSN-1 (both pancreatic) cells had fewer residualy gamma-H2AX foci than unsorted cells, pointing to radioresistance of CSLC. However, only MDA-MB-231 CSLC were more radioresistant than unsorted cells. Furthermore, MDA-MB-231 CSLC showed enhanced anchorage-independent growth and overexpression of activated Notch1 protein. The expression of cancer stem cell surface markers in the MDA-MB-231 xenograft model was increased after exposure to fractionated radiation. In contrast to PSN-1 cells, a growth advantage for MDA-MB-231 CSLC xenograft tumors was found compared to tumors arising from unsorted cells.Conclusions: CSLC subpopulations showed no general radioresistant phenotype, despite the quantities of CSLC subpopulations shown to correspond relatively well in other reports. Likewise, CSLC characteristics were found in some but not all of the tested cell lines. The reported problems in testing for CSLC in cell lines may be overcome by additional techniques, beyond sorting for markers. (C) 2009 Elsevier Inc.