Variant CD44 expression is enriching for a cell population with cancer stem cell-like characteristics in human lung adenocarcinoma.
Variant CD44 expression is enriching for a cell population with cancer stem cell-like characteristics in human lung adenocarcinoma.
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DOI：
10.7150/jca.19732
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发表时间：
2017
影响因子：
3.9
通讯作者：
Betsuyaku T
中科院分区：
文献类型：
--
作者：
Nishino M;Ozaki M;Hegab AE;Hamamoto J;Kagawa S;Arai D;Yasuda H;Naoki K;Soejima K;Saya H;Betsuyaku T
背景资料：初步研究已经确定了各种癌症中的癌症干细胞（CSC），并且有几项正在进行的针对这些细胞的临床研究。CD 44（标准或变体同种型）和/或醛脱氢酶（ALDH）表达是用于鉴定CSC的最常用标志物。本研究的目的是检查CD 44 v单独或与ALDH组合在人肺癌细胞系中鉴定CSC的能力。研究方法：我们研究了几种肺腺癌细胞系的能力，CD 44 v和/或ALDH表达，以丰富的CSC特性，如在体外差异增殖率，化疗耐药性，肿瘤球形成，和在体内致瘤性的细胞。我们还比较了它们的体内继发性肿瘤形成和异种移植肿瘤的组织学特征，并检查了它们的PD-L1、EGFR、xCT和活性氧（ROS）表达。结果如下：CD 44 v高/ALDH高和CD 44 v高/ALDH低细胞都富集在具有CSC特征的细胞中，其中CD 44 v高/ALDH低细胞更具增殖性且对化疗药物更具抗性，而CD 44 v高/ALDH高细胞在体外形成肿瘤球、制造原发性异种移植肿瘤和在体内增殖继发性肿瘤方面更有效。应用更严格的分选门来选择具有最高CD 44 v/ALDH表达的细胞导致CD 44 v高/ALDH低细胞失去其高增殖率和化疗抗性能力，但在CD 44 v高/ALDH高和CD 44 v高/ALDH低细胞中富集肿瘤球形成细胞。在H1650和HCC 827细胞中，CD 44 v高表达与PD-L1和xCT表达相关。在H1650细胞系中ALDH的表达没有改变这种关联。然而，在HCC 827细胞系中，ALDH表达与PD-L1呈负相关，与xCT表达呈正相关。结论：CD 44 v高表达的肺腺癌细胞富含CSCs。添加ALDH作为富集标记物赋予CD 44高/ALDH低细胞一些CSC特征，赋予CD 44高/ALDH高细胞其他CSC特征。我们认为肺腺癌中含有不同的CSC，每种CSC具有不同的特征。
Background: Preliminary studies have identified cancer stem cells (CSCs) in various cancers and there are several ongoing clinical studies targeting these cells. CD44 (standard or variant isoforms) and/or aldehyde dehydrogenase (ALDH) expression is the most commonly used markers for the identification of CSCs. The goal of the current study was to examine the ability of CD44v, either alone or in combination with ALDH, to identify CSCs within human lung cancer cells lines. Methods: We examined several lung adenocarcinoma cell lines for the ability of CD44v and/or ALDH expression to enrich for cells with CSC characteristics such as in vitro differential proliferation rate, chemotherapeutic-resistance, tumorsphere formation, and in vivo tumorigenicity. We also compared their in vivo secondary tumor formation, and histological characteristics of their xenograft tumors, and examined their expression of PD-L1, EGFR, xCT, and reactive oxygen species (ROS). Results: Both CD44vhigh/ALDHhigh and CD44vhigh/ALDHlow cells were enriched in cells with CSC characteristics, with the CD44vhigh/ALDHlow cells being more proliferative and more resistant to chemotherapeutics, whereas CD44vhigh/ALDHhigh cells were more efficient in forming tumorspheres in vitro, in making primary xenograft tumors, and in propagating secondary tumors in vivo. Applying stricter sorting gates to select for cells with the highest CD44v/ALDH expression caused the CD44vhigh/ALDHlow cells to lose their high proliferation rates and chemotherapeutic resistance ability, but enriched for the tumorsphere-forming cells among the CD44vhigh/ALDHhigh and CD44vhigh/ALDHlow cells. CD44vhigh expression was associated with PD-L1 and xCT expression in both H1650 and HCC827 cells. This association was not modified by ALDH expression in the H1650 cell line. However, in the HCC827 cell line, ALDH expression was negatively associated with PD-L1 and positively associated with xCT expression. Conclusion: Lung adenocarcinoma cells with high CD44v expression are enriched for CSCs. Addition of ALDH as an enrichment marker bestowed some CSCs characteristics to CD44vhigh/ALDHlow cells and others to CD44vhigh/ALDHhigh cells. We propose that lung adenocarcinoma contains different CSCs, each of them endowed with different CSC characteristics.
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DOI：
10.1111/resp.12094
发表时间：
2013-07
期刊：
Respirology (Carlton, Vic.)
影响因子：
--
作者：
Alamgeer M;Peacock CD;Matsui W;Ganju V;Watkins DN
通讯作者：
Watkins DN
CD44 剪接变体 v8-10 作为浆液性卵巢癌预后的标志。
影响因子：
3.7
作者：
Sosulski A;Horn H;Zhang L;Coletti C;Vathipadiekal V;Castro CM;Birrer MJ;Nagano O;Saya H;Lage K;Donahoe PK;Pépin D
通讯作者：
Pépin D
影响因子：
3.7
作者：
Aso, Takeichiro;Matsuo, Mioko;Masuda, Muneyuki
通讯作者：
Masuda, Muneyuki
影响因子：
--
作者：
Gay, Laura;Baker, Ann-Marie;Graham, Trevor A
通讯作者：
Graham, Trevor A
影响因子：
3.3
作者：
Liou GY;Storz P
通讯作者：
Storz P