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. 2009;11(4):R46.
doi: 10.1186/bcr2333. Epub 2009 Jul 9.

Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients

Bahriye Aktas  1 , Mitra Tewes, Tanja Fehm, Siegfried Hauch, Rainer Kimmig, Sabine Kasimir-Bauer
Affiliations

Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients

Bahriye Aktas et al. Breast Cancer Res. 2009.

Abstract

Introduction: The persistence of circulating tumor cells (CTC) in breast cancer patients might be associated with stem cell like tumor cells which have been suggested to be the active source of metastatic spread in primary tumors. Furthermore, these cells also may undergo phenotypic changes, known as epithelial-mesenchymal transition (EMT), which allows them to travel to the site of metastasis formation without getting affected by conventional treatment. Here we evaluated 226 blood samples of 39 metastatic breast cancer patients during a follow-up of palliative chemo-, antibody - or hormonal therapy for the expression of the stem cell marker ALDH1 and markers for EMT and correlated these findings with the presence of CTC and response to therapy.

Methods: 2 x 5 ml blood was analyzed for CTC with the AdnaTest BreastCancer (AdnaGen AG) for the detection of EpCAM, MUC-1 and HER2 transcripts. The recovered c-DNA was additionally multiplex tested for three EMT markers [Twist1, Akt2, PI3Kalpha] and separately for the tumor stem-cell markers ALDH1. The identification of EMT markers was considered positive if at least one marker was detected in the sample.

Results: 97% of 30 healthy donor samples investigated were negative for EMT and 95% for ALDH1 transcripts. CTC were detected in 69/226 (31%) cancer samples. In the CTC (+) group, 62% were positive for at least one of the EMT markers and 69% for ALDH1, respectively. In the CTC (-) group the percentages were 7% and 14%, respectively. In non-responders, EMT and ALDH1 expression was found in 62% and 44% of patients, in responders the rates were 10% and 5%, respectively.

Conclusions: Our data indicate that a major proportion of CTC of metastatic breast cancer patients shows EMT and tumor stem cell characteristics. Further studies are needed to prove whether these markers might serve as an indicator for therapy resistant tumor cell populations and, therefore, an inferior prognosis.

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Figures

Figure 1
Figure 1
Correlation of circulating tumor cells (CTCs) and response to therapy. Patients are stratified into responders and nonresponders.
Figure 2
Figure 2
Correlation of circulating tumor cells (CTCs), epidermal/mesenchymal transition (EMT) markers, and/or ALDH1. (a) The identification of EMT markers was considered positive if at least one marker was detected in the sample. (b) Detailed analysis for the correlation of CTC and ALDH1 as well as the EMT markers.
Figure 3
Figure 3
Correlation of epidermal/mesenchymal transition (EMT) markers or ALDH1 or both with response to therapy. (a) The identification of EMT markers was considered positive if at least one marker was detected in the sample. Patients are stratified into responders and nonresponders. (b) Detailed analysis for the correlation of ALDH1 as well as the EMT markers and response to therapy.
See this image and copyright information in PMC

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