Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines.
Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines.
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DOI：
10.1186/1471-2407-12-501
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发表时间：
2012-10-30
期刊：
影响因子：
3.8
通讯作者：
Untergasser G
中科院分区：
文献类型：
--
作者：
Martowicz A;Spizzo G;Gastl G;Untergasser G
上皮细胞粘附分子（EpCAM）已被证明在乳腺癌和干细胞中过表达，并已成为乳腺癌患者免疫治疗的有吸引力的靶点。本研究分析了EpCAM对具有上皮或间充质表型的乳腺癌细胞系的影响。为此，在具有上皮表型的EpCAM高乳腺癌细胞系（MCF-7、T47 D和SkBR 3）中进行了shRNA介导的EpCAM基因表达的敲低。此外，具有间充质表型的EpCAM低乳腺癌细胞系（MDA-MB-231，Hs 578 t）和EpCAM的可诱导过表达用于研究对增殖、迁移和体内生长的影响。与非特异性沉默对照（n/s-crtl）相比，EpCAM高细胞系中EpCAM（E#2）的敲低导致在血清减少的培养条件下细胞增殖减少。此外，胶原蛋白中3D培养条件下的DNA合成显著减少。具有EpCAM敲低的MCF-7和T47 D细胞的异种移植物形成侵袭性较低的较小肿瘤。具有四环素诱导的EpCAM过表达的EpCAM低细胞系在血清减少的生长条件下没有显示出增加的细胞增殖或迁移。具有EpCAM过表达的MDA-MB-231异种移植物显示对宿主组织的侵袭减少和鸡粒细胞的更多浸润。EpCAM在乳腺癌中的作用强烈依赖于肿瘤细胞的上皮或间充质表型。具有上皮表型的癌细胞需要EpCAM作为生长和侵袭促进因子，而具有间充质表型的肿瘤细胞在侵袭过程和肿瘤进展中不依赖EpCAM。这些发现可能对侵袭性乳腺癌患者中基于EpCAM的靶向策略具有临床意义。
The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAMhigh breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAMlow breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAMhigh cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAMlow cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer.
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影响因子：
168.9
作者：
Gastl, G;Spizzo, G;Mikuz, G
通讯作者：
Mikuz, G
影响因子：
3.5
作者：
Geraerts M;Willems S;Baekelandt V;Debyser Z;Gijsbers R
通讯作者：
Gijsbers R
影响因子：
50.3
作者：
Granot Z;Henke E;Comen EA;King TA;Norton L;Benezra R
通讯作者：
Benezra R
影响因子：
4.4
作者：
Harmon, BG
通讯作者：
Harmon, BG
DOI：
10.1073/pnas.1113744109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Cortez-Retamozo, Virna;Etzrodt, Martin;Pittet, Mikael J.
通讯作者：
Pittet, Mikael J.