The hypoxic microenvironment upgrades stem-like properties of ovarian cancer cells.
The hypoxic microenvironment upgrades stem-like properties of ovarian cancer cells.
复制标题
DOI：
10.1186/1471-2407-12-201
复制
发表时间：
2012-05-29
期刊：
影响因子：
3.8
通讯作者：
Suo Z
中科院分区：
文献类型：
--
作者：
Liang D;Ma Y;Liu J;Trope CG;Holm R;Nesland JM;Suo Z
目的：研究低氧是否影响卵巢癌细胞的干细胞性及其在低氧条件下的生物学行为。卵巢癌细胞株ES-2和OVCAR-3在不同氧分条件下培养，进行细胞增殖、细胞周期和侵袭能力分析。克隆形成实验和球体形成实验检测细胞的克隆形成能力。用流式细胞仪检测干细胞表面标志、SP、CD44bright和CD44dim细胞。免疫印迹法检测HIF-1α、HIF-2α、OT3/4和Sox2的蛋白表达。在低氧条件下培养的两株细胞生长相对缓慢，G0/G1期延长。然而，与常氧培养的细胞相比，在1%O2中预处理48 小时后，细胞的增殖率和渗透能力显著提高，克隆和球体明显增多。CD44bright细胞表达Oct3/4和Sox2的水平明显高于CD44dim细胞，并在体外形成明显更多的克隆和球体。低氧处理后，两株细胞CD44表达均增强，OVCAR-3细胞CD133表达增强。同时观察到ES-2和OVCAR-3细胞株的侧群(SP)细胞数量显著增加，Oct3/4和Sox2表达上调。我们的结论是，卵巢癌细胞通过上调干性相关因子来提升其干细胞样特性，从而在低氧条件下生存下来，并在被带回高氧环境时表现出更强的侵袭性。
To study whether hypoxia influences the stem-like properties of ovarian cancer cells and their biological behavior under hypoxia. Ovarian cancer cell lines ES-2 and OVCAR-3 were cultivated in different oxygen tensions for proliferation, cell cycling and invasion analyses. The clonogenic potential of cells was examined by colony formation and sphere formation assays. Stem cell surface markers, SP and CD44bright and CD44dim cells were analyzed by flow cytometry. Protein expression of HIF-1α, HIF-2α, Ot3/4 and Sox2 were investigated by Western blotting. Both cell lines cultivated at hypoxic condition grew relatively slowly with extended G0/G1 phase. However, if the cells were pre-treated under 1% O2 for 48 hrs before brought back to normoxia, the cells showed significantly higher proliferation rate with higher infiltration capability, and significant more colonies and spheres, in comparison to the cells always cultivated under normoxia. CD44bright cells expressed significantly higher levels of Oct3/4 and Sox2 than the CD44dim cells and formed significantly more clones and spheres examined in vitro. Hypoxic treatment of the cells resulted in stronger CD44 expression in both cell lines, and stronger CD133 expression in the OVCAR-3 cell line. In parallel with these findings, significantly increased number of side population (SP) cells and up-regulated expression of Oct3/4 and Sox2 in both ES-2 and OVCAR-3 cell lines were observed. We conclude that ovarian cancer cells survive hypoxia by upgrading their stem-like properties through up-regulation of stemness-related factors and behave more aggressively when brought back to higher oxygen environment.
登录
查看更多内容
影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
缺氧会增强乳腺癌中的 Notch 信号传导，导致 E-钙粘蛋白表达减少，细胞迁移和侵袭增加。
影响因子：
8.8
作者：
Chen, J.;Imanaka, N.;Chen, J.;Griffin, J. D.
通讯作者：
Griffin, J. D.
影响因子：
4.3
作者：
Henze, Anne-Theres;Acker, Till
通讯作者：
Acker, Till
影响因子：
1
作者：
Gao, Quanli;Geng, Li;Suo, Zhenhe
通讯作者：
Suo, Zhenhe
影响因子：
4.3
作者：
Higgins, L. H.;Withers, H. G.;Moyes, C. D.
通讯作者：
Moyes, C. D.