Extensive characterization of sphere models established from colorectal cancer cell lines
Extensive characterization of sphere models established from colorectal cancer cell lines
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DOI：
10.1007/s00018-012-1160-9
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发表时间：
2013-02-01
影响因子：
8
通讯作者：
Duval, Alex
中科院分区：
文献类型：
--
作者：
Collura, Ada;Marisa, Laetitia;Duval, Alex
癌症和干细胞之间的联系已经提出了很多年。随着癌症干细胞（CSC）理论的广泛研究，开发了新的方法来培养和扩增具有保守的“干细胞性”决定因素的癌细胞。这些细胞显示出在补充有生长因子和化学物质的无血清培养基中作为球体悬浮生长的能力增加。这种现象在已建立的癌细胞系中的生理相关性仍不清楚。传统上，细胞系被用于探索肿瘤生物学，并作为筛选潜在治疗药物的临床前模型。在这里，我们从25个已建立的结直肠癌细胞系中培养细胞形成球（CFS）。将CFS的分子和细胞特征与肿瘤细胞进行比较。CFS可从72%的细胞系中分离到. CFS及其亲本CRC细胞系均具有高度致瘤性。与其亲代细胞相比，它们显示出类似的推定CSC标记物表达。CRC细胞作为CFS生长的能力通过预先用5-氟尿嘧啶处理而大大增强。在分子水平上，CFS和亲本CRC细胞显示出相同的基因突变和非常相似的基因组谱，尽管微阵列分析显示CFS基因表达的变化与DNA拷贝数无关。我们从所有CRC细胞系中鉴定出CFS共有的CFS基因表达特征，其可预测CRC患者的疾病复发。总之，衍生自CRC细胞系的CFS模型具有有趣的表型特征，其可能与耐药性和疾病复发具有临床相关性。
Links between cancer and stem cells have been proposed for many years. As the cancer stem cell (CSC) theory became widely studied, new methods were developed to culture and expand cancer cells with conserved determinants of "stemness". These cells show increased ability to grow in suspension as spheres in serum-free medium supplemented with growth factors and chemicals. The physiological relevance of this phenomenon in established cancer cell lines remains unclear. Cell lines have traditionally been used to explore tumor biology and serve as preclinical models for the screening of potential therapeutic agents. Here, we grew cell-forming spheres (CFS) from 25 established colorectal cancer cell lines. The molecular and cellular characteristics of CFS were compared to the bulk of tumor cells. CFS could be isolated from 72 % of the cell lines. Both CFS and their parental CRC cell lines were highly tumorigenic. Compared to their parental cells, they showed similar expression of putative CSC markers. The ability of CRC cells to grow as CFS was greatly enhanced by prior treatment with 5-fluorouracil. At the molecular level, CFS and parental CRC cells showed identical gene mutations and very similar genomic profiles, although microarray analysis revealed changes in CFS gene expression that were independent of DNA copy-number. We identified a CFS gene expression signature common to CFS from all CRC cell lines, which was predictive of disease relapse in CRC patients. In conclusion, CFS models derived from CRC cell lines possess interesting phenotypic features that may have clinical relevance for drug resistance and disease relapse.