Biological heterogeneity of putative bladder cancer stem-like cell populations from human bladder transitional cell carcinoma samples
Biological heterogeneity of putative bladder cancer stem-like cell populations from human bladder transitional cell carcinoma samples
复制标题
DOI：
10.1111/j.1349-7006.2009.01414.x
复制
发表时间：
2010-02-01
期刊：
影响因子：
5.7
通讯作者：
Dalpra, Leda
中科院分区：
文献类型：
--
作者：
Bentivegna, Angela;Conconi, Donatella;Dalpra, Leda
移行细胞癌（TCC）是最常见的膀胱癌类型。新出现的证据表明，肿瘤生长和繁殖的能力依赖于一小部分细胞，即癌症干细胞样细胞（CSCs）或肿瘤起始细胞。我们报道了从原发性tcc中分离和推测膀胱CSC群体的生物学特性。分离细胞在干细胞培养条件下（含有丝分裂生长因子的无血清培养基）被诱导增殖。增殖细胞形成球状体（尿球），并测定其广泛增殖和自我更新的能力。他们的几种干细胞标记物（CD133、Oct-3/4、巢蛋白和细胞角蛋白）的阳性也通过免疫荧光试验进行了评估，它们可能在血清存在下具有分化的潜力。在干细胞培养条件下，它们逐渐表现出增殖丧失、粘附底物和形态变化，这可能反映了它们逐渐获得分化能力和自我更新能力的丧失。为了评估分离后是否发生了有效的细胞选择，在分离后和培养后立即进行了新鲜染色体扩散的常规细胞遗传学研究。此外，用UroVysion法对石蜡包埋组织切片、新鲜细胞核和培养后细胞核进行分子细胞遗传学研究。收集到的数据表明，重要的核型变化和对低二倍体或近二倍体细胞的积极选择，失去了新肿瘤中存在的复杂性。（癌症科学2010；101:416-424）
Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of cells, the cancer stem-like cells (CSCs) or tumor initiating cells. We report on the isolation and biological characterization of putative bladder CSC populations from primary TCCs. Isolated cells were induced to proliferate in stem cell culture conditions (serum-free medium containing mitogenic growth factors). The proliferating cells formed spheroids (urospheres) and their abilities for extensive proliferation and self-renewal were assayed. Their positivity for several stem cell markers (CD133, Oct-3/4, nestin, and cytokeratins) was also assessed by immunofluorescence tests and they could have the potential to differentiate in the presence of serum. In stem cell culture conditions they gradually showed loss of proliferation, adherence to the substrate, and morphological changes, which might reflect their progressive acquisition of differentiative capacity and loss of self-renewal ability. To evaluate if effective cell selection occurred after isolation, conventional cytogenetic studies on fresh chromosome spreads immediately after isolation and after culture were carried out. In addition, a molecular cytogenetic study by UroVysion assay was carried out on paraffin-embedded tissue sections and on fresh and after culture nuclei preparations. The data collected indicated important karyotype changes and a positive selection for hypo- or near-diploid cells, losing the complexity present in fresh tumors. (Cancer Sci 2010; 101: 416-424)