Tumor Pathophysiology, OncoRay-Center for Radiation Research in Oncology, Dresden University of Technology, Germany.
Radiother Oncol. 2009 Sep;92(3):353-61. doi: 10.1016/j.radonc.2009.06.034. Epub 2009 Aug 21.
CD133 is controversially discussed as putative (surrogate) marker for cancer stem/tumor-initiating cell populations (CSC/TIC) in epithelial tumors including colorectal carcinomas (CRCs). We studied CD133 expression in established CRC cell lines and examined in vitro behavior, radioresponse and in vivo tumor formation of CD133(+/-) subpopulations of one cell line of interest.
Ten CRC cell lines were analyzed for CD133 expression using flow cytometry and Western blotting. CD133+ and CD133(-) HCT-116 subpopulations were separated by FACS and studied in 2-D and 3-D culture and colony formation assays after irradiation. Subcutaneous xenograft formation was monitored in NMRI (nu/nu) mice.
CRC cell lines could be classified into three groups: (i) CD133(-), (ii) CD133+ and (iii) those with two distinct CD133+ and CD133(-) subpopulations. Isolated CD133(+/-) HCT-116 subpopulations were studied relative to the original fraction. No difference was found in 2-D growth, spheroid formation or radioresponse in vitro. Also, tumor formation and growth rate did not differ for the sorted subpopulations. However, a subset of xenografts originated from CD133(-) HCT-116 showed a striking enrichment in the CD133+ fraction. Our data show that CD133 expression is not selective for sphere forming, tumor-initiating or radioresistant subpopulations in the HCT-116 CRC cell lines. This implies that CD133 cannot be regarded as a CSC/TIC marker in all CRC cell lines and that functional measurements of tumor formation have to generally accompany CSC/TIC-directed mechanistic or therapeutic studies.
CD133 作为上皮肿瘤（包括结直肠癌）中癌症干细胞/肿瘤起始细胞群（CSC/TIC）的假定（替代）标志物，存在争议。我们研究了已建立的结直肠癌细胞系中 CD133 的表达，并研究了一个感兴趣细胞系的 CD133(+/-)亚群的体外行为、放射反应和体内肿瘤形成。
使用流式细胞术和 Western blot 分析了 10 种结直肠癌细胞系中 CD133 的表达。通过 FACS 分离 CD133+和 CD133(-)HCT-116 亚群，并在照射后进行 2-D 和 3-D 培养和集落形成测定。监测 NMRI（nu/nu）小鼠皮下异种移植的形成。
CRC 细胞系可分为三组：（i）CD133(-)，（ii）CD133+和（iii）具有两个不同的 CD133+和 CD133(-)亚群。与原始部分相比，研究了分离的 CD133(+/-)HCT-116 亚群。在体外，2-D 生长、球体形成或放射反应没有差异。此外，分选的亚群的肿瘤形成和生长速度没有差异。然而，源自 CD133(-)HCT-116 的一部分异种移植物在 CD133+亚群中明显富集。我们的数据表明，CD133 表达不是 HCT-116 CRC 细胞系中球体形成、肿瘤起始或放射抵抗亚群的选择性标志物。这意味着 CD133 不能被视为所有 CRC 细胞系中的 CSC/TIC 标志物，并且 CSC/TIC 定向的机制或治疗研究通常需要伴随肿瘤形成的功能测量。
