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PMID: 19589136 Published · ppublish English Journal Article

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

Breast cancer research : BCR ·Vol. 11 ·No. 4 ·2009-00-00 ·Pages R46

Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S

Abstract

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. 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. 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. 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.

MeSH Terms
Adult Aged Aldehyde Dehydrogenase/analysis Aldehyde Dehydrogenase 1 Family Antigens, CD34/analysis Antigens, Differentiation/analysis Biomarkers Biomarkers, Tumor/analysis Breast Neoplasms/blood,chemistry,pathology Carcinoma, Ductal, Breast/blood,chemistry,pathology,secondary Cell Line, Tumor/chemistry Cell Transdifferentiation Epithelial Cells/chemistry,pathology Female Humans Isoenzymes/analysis Mesoderm/chemistry,pathology Middle Aged Neoplasm Proteins/analysis Neoplastic Cells, Circulating/chemistry Neoplastic Stem Cells/chemistry Ovarian Neoplasms/chemistry,pathology Retinal Dehydrogenase Young Adult
Chemicals
Antigens, CD34 Antigens, Differentiation Biomarkers Biomarkers, Tumor Isoenzymes Neoplasm Proteins Aldehyde Dehydrogenase 1 Family Aldehyde Dehydrogenase ALDH1A1 protein, human Retinal Dehydrogenase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Aktas Bahriye
Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany. bahriye.aktas@uk-essen.de
Tewes Mitra
Fehm Tanja
Hauch Siegfried
Kimmig Rainer
Kasimir-Bauer Sabine
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Article Info
Journal
Breast cancer research : BCR
Abbr.
Breast Cancer Res
ISSN
1465-542X
DOI
10.1186/bcr2333
Email
bahriye.aktas@uk-essen.de
Published
2009-00-00
Epub
2009-00-09
Pages
R46
Language
English
Region
England
NLM ID
100927353
PMCID
PMC2750105
Subset
IM
External Links
PubMed source DOI: 10.1186/bcr2333 PMC Full Text View journal details
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