Two-dimensional differential gel electrophoresis of a cell line derived from a breast cancer micrometastasis revealed a stem/ progenitor cell protein profile.
Dissemination of primary cancer cells to distant sites is an early event in breast cancer. These cells can invade the bone marrow, rest there, and many years later disseminated tumor cells (DTC) can grow out to form overt metastases. Epithelium specific cytokeratins are commonly used as marker proteins for sensitive detection of metastatic lesions. However, due to difficulties in the detection of DTC, the question arises if DTC necessarily have the same protein expression profile as advanced tumors. On that account, we analyzed the previously uncharacterized breast cancer DTC cell line BC-M1 by 2-D DIGE. Special protein concentration and purification protocols for 2-DE were developed which resulted in high recovery rates and increased display of alkaline proteins. A broad range reference map of metastasis relevant proteins was compiled including the cytokeratins 5, 7, 8, 17, 18, and 19 and several classes of cytoskeleton proteins involved in metastasis like ezrin, gelsolin, vinculin, or vimentin. BC-M1 shows the rare and highly metastatic vimentin/cytokeratin 5 positive and cytokeratin 8/18 negative breast cancer phenotype and expresses Her-2, which is also found in stem cells/progenitor cells of primary tumors. Supported by the detection of several other epithelium-derived proteins, the example BC-M1 indicates that the protein expression profile of DTC might be reminiscent of the expression profile of the early tumor, which differs from the advanced tumor. Hence, DTC from breast cancer patients' bone marrow expressed cytokeratin 5, which further supports our hypothesis.
Bartkowiak
Kai
K
Institute for Tumor Biology, University Medical Center Hamburg-Eppendorf Martinistr. 52, 20246 Hamburg, Germany.
Wieczorek
Marek
M
Buck
Friedrich
F
Harder
Sönke
S
Moldenhauer
Jennifer
J
Effenberger
Katharina E
KE
Pantel
Klaus
K
Peter-Katalinic
Jasna
J
Brandt
Burkhard H
BH
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
D009363:Neoplasm Proteins; D020543:Proteome