Changes in cytoskeletal protein composition indicative of an epithelial-mesenchymal transition in human micrometastatic and primary breast carcinoma cells
| Autor: | Klaus Pantel, Guido Sauter, Ute Woelfle, Volker Assmann, Thomas Rau, Sabine Riethdorf, Birthe Willipinski-Stapelfeldt, Jochen Heukeshoven |
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| Rok vydání: | 2005 |
| Předmět: |
CA15-3
Proteomics Cancer Research Pathology medicine.medical_specialty Mitotic index Proteome Breast Neoplasms Biology Epithelium Mesoderm Cytokeratin Breast cancer Intermediate Filament Proteins Cancer stem cell Cell Line Tumor medicine Humans Vimentin Electrophoresis Gel Two-Dimensional Epithelial–mesenchymal transition Neoplasm Metastasis skin and connective tissue diseases Cell Line Transformed medicine.disease Prognosis Immunohistochemistry Survival Analysis Cytoskeletal Proteins Oncology Tissue Array Analysis Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Cancer cell Multivariate Analysis Keratins Female Breast carcinoma |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 11(22) |
| ISSN: | 1078-0432 |
| Popis: | Purpose: The bone marrow is a frequent and clinically important homing site for early disseminated breast cancer cells. Here, we aimed to profile the protein expression of these cells using unique cell line models and to evaluate the prognostic relevance of candidate gene expression for breast cancer patients. Experimental Design: To identify expression patterns characteristic for micrometastatic cells, three different cell lines (BC-K1, BC-P1, and BC-S1) established by SV40 immortalization of cancer cells isolated from the bone marrow of patients with breast cancer were compared with MCF-7 breast cancer and SV40 immortalized normal breast ductal cells (MTSV-1.7) using two-dimensional gel electrophoresis followed by MALDI-ToF analysis. The prognostic significance and clinicopathologic associations of selected differentially expressed proteins were evaluated using high-density breast cancer tissue microarrays. Results: In contrast to MCF-7 and MTSV1-7 reference cell lines, all micrometastatic cancer cell lines displayed loss of epithelial cytokeratins (CK8, CK18, and CK19) and ectopic expression of vimentin commonly present in mesenchymal cells. Immunohistochemical analysis of 2,517 samples of breast cancer further showed that loss of cytokeratin and ectopic vimentin expression were significantly associated with a higher tumor grade, high mitotic index, and negative estrogen/progesterone-receptor status. Although in univariate analyses significantly related to clinical outcome, none of the cytokeratins analyzed were independently associated with either overall or cancer-specific survival. Conclusions: Micrometastatic cancer cells exhibit marked changes in the expression pattern of cytoskeletal proteins indicative of an epithelial-mesenchymal transition. This phenotypical change could already be detected in primary tumors and is associated with the aggressive behavior of breast cancer cells in vivo. |
| Databáze: | OpenAIRE |
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