ABSTRACT
The aim of this study is to determine whether circulating epithelial cells (CEC) detected in patients with differentiated thyroid cancer (DTC) stem from the thyroid gland. CEC have been described to increase in patients with progressive cancer disease and thus have been used as a marker of tumour cell dissemination. CEC were selected from venous blood samples of five DTC patients and analysis of thyroid-specific mRNA (i.e. Tg, TSH-R, TPO, NIS) was performed on a single cell level. 16/48 cells were positive for at least three different thyroid-mRNA transcripts, predominantly found in patients with detectable serum thyroglobulin. In conclusion, evidence was found that in patients with detectable serum thyroglobulin, most of the CECs originate from the thyroid gland. However, further investigations including a larger sample size are needed to validate the clinical impact of this method.
Subject(s)
Biomarkers, Tumor/genetics , Cell Differentiation , Epithelial Cells/pathology , Neoplastic Cells, Circulating/pathology , RNA, Messenger/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Antigens, Neoplasm/genetics , Antigens, Neoplasm/metabolism , Autoantigens/genetics , Autoantigens/metabolism , Biomarkers, Tumor/metabolism , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Epithelial Cell Adhesion Molecule , Epithelial Cells/metabolism , Humans , Iodide Peroxidase/genetics , Iodide Peroxidase/metabolism , Iron-Binding Proteins/genetics , Iron-Binding Proteins/metabolism , Neoplastic Cells, Circulating/metabolism , Real-Time Polymerase Chain Reaction , Receptors, Thyrotropin/genetics , Receptors, Thyrotropin/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Symporters/genetics , Symporters/metabolism , Tumor Cells, CulturedABSTRACT
Although considerable progress has been achieved in breast cancer diagnosis and treatment, the live-saving effect of mammography has hardly been measurable and the benefit of taxanes regarded as highly active is still a matter of debate, possibly because treatment effects have hitherto been mainly determined from the solid part of the tumor, due to lack of measurability of the systemic part of the disease. Here, we have quantified the influence on the systemic disease, cells mobilized from the solid tumor. Increased numbers of circulating epithelial cells were observed in screened individuals and still higher numbers in breast cancer patients with repeated mammograms as compared to mammogram naïve individuals. Taxanes as part of the subsequent systemic treatment led to mobilization of tumor suspect cells in up to 78% cases and the majority of relapses have occurred in these patients. Surgery-induced activation of disseminated cells may additionally contribute to metastasis formation.
ABSTRACT
BACKGROUND: The epithelial cell adhesion molecule (EpCAM) embedded in the plasma membrane of circulating epithelial tumor cells (CETC) is used for detection and enrichment of circulating tumor cells in peripheral blood and as a target for anti-epithelial antibodies elicited during immune response in anti-tumor immunization. Although an efficient immune response against EpCAM can be generated, the clinical application of such approaches has not been successful so far and the detection of circulating epithelial cells is highly variable. One reason for these discrepancies may be that not all circulating tumor cells are equally accessible for the specific antibody. A possible reason might be masking of EpCAM by glycoproteins or membrane lipoproteins preventing antibody binding. METHODS: We have tested the application of detergents as demasking agents known to be successful in demasking red blood cell epitopes and determined how and in which way they affect integral membrane proteins and membrane lipids. RESULTS: The results showed that the polysorbate Tween®20, a non-ionic detergent like organic solvent is able to demask EpCAM on CETC and makes it better accessible to its specific antibody retaining at the same time full cell viability. CONCLUSIONS: The data presented in this study suggest that EpCAM is present on part of circulating tumor cells in a masked form and that it is possible to demask EpCAM on CETC of breast cancer patients using Tween®20 treatment. But further studies are needed to elucidate the mechanism of demasking.