Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties.
Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties.
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表达 CD44 的非小细胞肺癌细胞富含干细胞样特性。
DOI：
10.1371/journal.pone.0014062
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发表时间：
2010-11-19
期刊：
影响因子：
3.7
通讯作者：
Wong, Maria Pik
中科院分区：
文献类型：
--
作者：
Leung, Elaine Lai-Han;Fiscus, Ronald R.;Tung, James W.;Tin, Vicky Pui-Chi;Cheng, Lik Cheung;Sihoe, Alan Dart-Loon;Fink, Louis M.;Ma, Yupo;Wong, Maria Pik
癌症干细胞理论假设癌症是由具有自我更新和其他干细胞样特性的癌症干细胞（CSC）或肿瘤起始细胞（TIC）延续的，而分化的非干细胞/起始细胞具有有限的寿命。为了研究这一假设是否适用于肺癌，识别肺CSC并证明这些能力是必不可少的。采用流式细胞术检测10株肺癌细胞系中5种干细胞标志物（CD 34、CD 44、CD 133、BMI 1和OCT 4）的表达谱。通过测试体外和体内致瘤性进一步研究了CD 44。4个细胞系的CD 44+细胞均具有球体形成和体内肿瘤发生能力。用H1299细胞系证明了裸鼠体内肿瘤的可移植性。从CD 44+细胞开始的原代异种移植物由混合的CD 44+和CD 44 −细胞组成，其比例与亲本H1299细胞系相似，支持体内分化。半定量实时PCR（RT-PCR）显示，新鲜分选的CD 44+和来自CD 44+起始肿瘤的CD 44+细胞均表达多能性基因OCT 4/POU 5 F1、NANOG、SOX 2。这些干细胞标记物不被CD 44 −细胞表达。此外，新鲜分选的CD 44+细胞比CD 44 −细胞对顺铂治疗更具抗性，凋亡水平较低。141例手术切除的非小细胞肺癌的免疫组化分析显示，50.4%的肿瘤细胞表达CD 44，而无CD 34，并且在肿瘤细胞中观察到CD 133的表达。CD 44表达与鳞状细胞癌相关，但出乎意料的是，在表达CD 44的腺癌中观察到更长的生存期。总之，我们的研究结果表明，干细胞样的特性是丰富的CD 44表达的一些肺癌细胞系的亚群。需要进一步的研究来阐明CD 44在体内环境中肿瘤细胞更新和癌症传播中的作用。
The cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these capacities is essential. The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) were screened by flow cytometry in 10 lung cancer cell lines. CD44 was further investigated by testing for in vitro and in vivo tumorigenecity. Formation of spheroid bodies and in vivo tumor initiation ability were demonstrated in CD44+ cells of 4 cell lines. Serial in vivo tumor transplantability in nude mice was demonstrated using H1299 cell line. The primary xenografts initiated from CD44+ cells consisted of mixed CD44+ and CD44− cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44+ and CD44+ cells derived from CD44+-initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2. These stemness markers were not expressed by CD44− cells. Furthermore, freshly sorted CD44+ cells were more resistant to cisplatin treatment with lower apoptosis levels than CD44− cells. Immunohistochemical analysis of 141 resected non-small cell lung cancers showed tumor cell expression of CD44 in 50.4% of tumors while no CD34, and CD133 expression was observed in tumor cells. CD44 expression was associated with squamous cell carcinoma but unexpectedly, a longer survival was observed in CD44-expressing adenocarcinomas. Overall, our results demonstrated that stem cell-like properties are enriched in CD44-expressing subpopulations of some lung cancer cell lines. Further investigation is required to clarify the role of CD44 in tumor cell renewal and cancer propagation in the in vivo environment.
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人类胚胎干细胞，结肠癌和黑色素瘤细胞系中CD133表位的细胞周期依赖性变化。
影响因子：
11.2
作者：
Jaksch, Marie;Munera, Jorge;Bajpai, Ruchi;Terskikh, Alexey;Oshima, Robert G.
通讯作者：
Oshima, Robert G.
CD44+ CD24（ - ）前列腺细胞是早期的癌症祖/干细胞，为预后不良的患者提供了模型。
影响因子：
8.8
作者：
Hurt, E. M.;Kawasaki, B. T.;Klarmann, G. J.;Thomas, S. B.;Farrar, W. L.
通讯作者：
Farrar, W. L.
影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
4.8
作者：
Bourguignon, Lilly Y. W.;Gilad, Eli;Peyrollier, Karine
通讯作者：
Peyrollier, Karine
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.