TGF-β1 exposure induces epithelial to mesenchymal transition both in CSCs and non-CSCs of the A549 cell line, leading to an increase of migration ability in the CD133+ A549 cell fraction.
TGF-β1 exposure induces epithelial to mesenchymal transition both in CSCs and non-CSCs of the A549 cell line, leading to an increase of migration ability in the CD133+ A549 cell fraction.
复制标题
DOI：
10.1038/cddis.2013.144
复制
发表时间：
2013-05-02
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
转移是癌症死亡的主要原因。非小细胞肺癌（NSCLC）占原发性恶性肺肿瘤的近85%。近年来的研究表明，上皮-间质转化（epithelial-to-mesenchymal transition， EMT）在癌细胞转移的早期过程中起着关键作用。转化生长因子-β1 （TGF-β1）是EMT的主要诱导剂。本研究旨在探讨TGF-β1对A549细胞系中CD133阳性细胞的肿瘤干细胞（CSCs）、侧群（SP）和CD133阴性细胞的非肿瘤干细胞（non-CSCs）和SP的影响。我们证明TGF-β1在CSC和非CSC A549亚群中诱导EMT，上调vimentin和Slug等间质标记物的表达，下调e-cadherin和细胞角蛋白等上皮标记物的水平。除CD133−细胞外，接受EMT的CSC和非CSC A549子细胞表现出强烈的迁移和高水平的MMP9。OCT4水平在除CD133−细胞外的所有细胞组分中均强烈上调。相反，伤口大小显示TGF-β1增强了野生型A549以及CD133+和SP+细胞的运动性。对于CD133−和SP−细胞，TGF-β1暴露不改变其运动性。最后，对生长动力学的评估揭示了CD133+ A549细胞的主要集落形成效率。其中，SP+和SP−A549细胞的集落形成效率高于未处理的相应细胞，而CD133−细胞暴露于TGF-β1后，其集落数量未见变化。我们的结论是，有可能突出不同的细胞亚群与不同等级的干性。每个群体似乎都参与了不同的生物学机制，如干性维持、致瘤性、入侵和迁移。
Metastasis is the leading cause of death by cancer. Non-small-cell lung cancer (NSCLC) represents nearly 85% of primary malignant lung tumours. Recent researches have demonstrated that epithelial-to-mesenchymal transition (EMT) plays a key role in the early process of metastasis of cancer cells. Transforming growth factor-β1 (TGF-β1) is the major inductor of EMT. The aim of this study is to investigate TGF-β1's effect on cancer stem cells (CSCs) identified as cells positive for CD133, side population (SP) and non-cancer stem cells (non-CSCs) identified as cells negative for CD133, and SP in the A549 cell line. We demonstrate that TGF-β1 induces EMT in both CSC and non-CSC A549 sublines, upregulating the expression of mesenchymal markers such as vimentin and Slug, and downregulating levels of epithelial markers such as e-cadherin and cytokeratins. CSC and non-CSC A549 sublines undergoing EMT show a strong migration and strong levels of MMP9 except for the CD133− cell fraction. OCT4 levels are strongly upregulated in all cell fractions except CD133− cells. On the contrary, wound size reveals that TGF-β1 enhances motility in wild-type A549 as well as CD133+ and SP+ cells. For CD133− and SP− cells, TGF-β1 exposure does not change the motility. Finally, assessment of growth kinetics reveals major colony-forming efficiency in CD133+ A549 cells. In particular, SP+ and SP− A549 cells show more efficiency to form colonies than untreated corresponding cells, while for CD133− cells no change in colony number was observable after TGF-β1 exposure. We conclude that it is possible to highlight different cell subpopulations with different grades of stemness. Each population seems to be involved in different biological mechanisms such as stemness maintenance, tumorigenicity, invasion and migration.
登录
查看更多内容
影响因子：
6
作者：
Rosivatz, E;Becker, I;Becker, KF
通讯作者：
Becker, KF
影响因子：
3.7
作者：
Pirozzi G;Tirino V;Camerlingo R;Franco R;La Rocca A;Liguori E;Martucci N;Paino F;Normanno N;Rocco G
通讯作者：
Rocco G
影响因子：
50.3
作者：
Labelle M;Begum S;Hynes RO
通讯作者：
Hynes RO
DOI：
10.1186/bcr778
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Brown KA;Aakre ME;Gorska AE;Price JO;Eltom SE;Pietenpol JA;Moses HL
通讯作者：
Moses HL
影响因子：
8
作者：
Collura, Ada;Marisa, Laetitia;Duval, Alex
通讯作者：
Duval, Alex