The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer
The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer
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DOI：
10.1016/j.ejcts.2009.03.063
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发表时间：
2009-09-01
影响因子：
3.4
通讯作者：
Pirozzi, Giuseppe
中科院分区：
文献类型：
--
作者：
Tirino, Virginia;Camerlingo, Rosa;Pirozzi, Giuseppe
目的：新出现的证据表明，在大部分肿瘤中具有干细胞特征的特定癌细胞亚群与异质性恶性肿瘤的发病机制有关。驱动肿瘤生长的细胞被称为癌症起始细胞或癌症干细胞（下文称为CSC）。CSC最初从白血病中分离，随后从几种实体瘤中分离，包括脑癌、乳腺癌、前列腺癌、结肠癌和肺癌。本研究旨在分离和鉴定非小细胞肺癌（NSCLC）中的肿瘤起始细胞群。方法：对那不勒斯国家癌症研究所89例接受肿瘤切除术的NSCLC标本进行分析。采用三种方法分离肿瘤起始细胞：（1）流式细胞术分析鉴定表面标志物如CD 24、CD 29、CD 31、CD 34、CD 44、CD 133和CD 326的阳性细胞;（2）Hoechst 33342染料排除试验鉴定干细胞存在的侧群特征;（3）非贴壁培养条件能够形成具有干细胞样特征的球体。通过软琼脂测定和注射到NOD/SCID小鼠中的细胞的致瘤潜力的定义用于功能性地定义（体外和体内）从NSCLC样品分离的推定的CSC。结果如下：对NSCLC样本进行流式细胞术分析后，在分析的89份新鲜标本中，72%的标本中发现了CD 133阳性细胞，平均占总细胞的6%。此外，CD 133阳性细胞的数量显着增加时，从NSCLC标本中分离的细胞，在非贴壁培养条件下生长为球体。当在软琼脂中测定时，来自NSCLC的细胞以球体生长，在培养物中产生3.8倍的集落数量，并且与相应的贴壁细胞相比，在非肥胖糖尿病（NOD）/严重联合免疫缺陷（SCID）小鼠中的致瘤性更高。结论：我们已经从非小细胞肺癌中分离出一群CD 133阳性细胞，并对其进行了表征，这些细胞能够产生球体，并可以作为肿瘤起始细胞。(C)2009年欧洲胸外科协会。Elsevier B. V.出版，保留所有权利。
Objective: Emerging evidence suggests that specific sub-populations of cancer cells with stem cell characteristics within the bulk of tumours are implicated in the pathogenesis of heterogeneous malignant tumours. The cells that drive tumour growth have been denoted cancer-initiating cells or cancer stem cells (hereafter CSCs). CSCs have been isolated initially from leukaemias and subsequently from several solid tumours including brain, breast, prostate, colon and lung cancer. This study aimed at isolating and characterising the population of tumour-initiating cells in non-small-cell lung cancer (NSCLC). Methods: Specimens of NSCLC obtained from 89 patients undergoing tumour resection at the Cancer National Institute of Naples were analysed. Three methods to isolate the tumour-initiating cells were used: (1) flow cytometry analysis for identification of positive cells for surface markers such as CD24, CD29, CD31, CD34, CD44, CD133 and CD326; (2) Hoechst 33342 dye exclusion test for the identification of a side-population characteristic for the presence of stem cells; (3) non-adherent culture condition able to form spheres with stem cell-like characteristics. Definition of the tumourigenic potential of the cells through soft agar assay and injection into NOD/SCID mice were used to functionally define (in vitro and in vivo) putative CSCs isolated from NSCLC samples. Results: Upon flow cytometry analysis of NSCLC samples, CD133-positive cells were found in 72% of 89 fresh specimens analysed and, on average, represented 6% of the total cells. Moreover, the number of CD133-positive cells increased markedly when the cells, isolated from NSCLC specimens, were grown as spheres in non-adherent culture conditions. Cells from NSCLC, grown as spheres, when assayed in soft agar, give rise to a 3.8-fold larger number of colonies in culture and are more tumourigenic in non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice compared with the corresponding adherent cells. Conclusions: We have isolated and characterised a population of CD133-positive cells from NSCLC that is able to give rise to spheres and can act as tumour-initiating cells. (C) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.