Abstract | BACKGROUND: METHODS: 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. RESULTS: 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. CONCLUSIONS: 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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Authors | Agnieszka Martowicz, Gilbert Spizzo, Guenther Gastl, Gerold Untergasser |
Journal | BMC cancer
(BMC Cancer)
Vol. 12
Pg. 501
(Oct 30 2012)
ISSN: 1471-2407 [Electronic] England |
PMID | 23110550
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Neoplasm
- Cadherins
- Cell Adhesion Molecules
- Epithelial Cell Adhesion Molecule
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Topics |
- Animals
- Antigens, Neoplasm
(genetics, metabolism)
- Blotting, Western
- Breast Neoplasms
(genetics, metabolism, pathology)
- Cadherins
(genetics, metabolism)
- Cell Adhesion Molecules
(genetics, metabolism)
- Cell Line
- Cell Line, Tumor
- Cell Movement
(genetics)
- Cell Proliferation
- Cells, Cultured
- Chick Embryo
- Chorioallantoic Membrane
(metabolism, pathology)
- Epithelial Cell Adhesion Molecule
- Gene Expression Regulation, Neoplastic
- HEK293 Cells
- Humans
- Immunohistochemistry
- Neoplasm Invasiveness
- Neoplasms, Experimental
(genetics, metabolism, pathology)
- Phenotype
- RNA Interference
- Reverse Transcriptase Polymerase Chain Reaction
- Xenograft Model Antitumor Assays
(methods)
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