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Multiparameter analysis, including EMT markers, on negatively enriched blood samples from patients with squamous cell carcinoma of the head and neck
- Source :
- PLoS ONE, Vol 7, Iss 7, p e42048 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Epithelial to mesenchymal transition (EMT) has been hypothesized as a mechanism by which cells change phenotype during carcinogenesis, as well as tumor metastasis. Whether EMT is involved in cancer metastasis has a specific, practical impact on the field of circulating tumor cells (CTCs). Since the generally accepted definition of a CTC includes the expression of epithelial surface markers, such as EpCAM, if a cancer cell loses its epithelial surface markers (which is suggested in EMT), it will not be separated and/or identified as a CTC. We have developed, and previously reported on the use of, a purely negative enrichment technology enriching for CTCs in the blood of squamous cell carcinoma of the head and neck (SCCHN). This methodology does not depend on the expression of surface epithelial markers. Using this technology, our initial data on SCCHN patient blood indicates that the presence of CTCs correlates with worse disease-free survival. Since our enrichment is not dependent on epithelial markers, we have initiated investigation of the presence of mesenchymal markers in these CTC cells to include analysis of: vimentin, epidermal growth factor receptor, N-cadherin, and CD44. With the aid of confocal microscopy, we have demonstrated not only presumed CTCs that express and/or contain: a nucleus, cytokeratins, vimentin, and either EGFR, CD44, or N-cadherin, but also cells that contain all of the aforementioned proteins except cytokeratins, suggesting that the cells have undergone the EMT process. We suggest that our negative depletion enrichment methodology provides a more objective approach in identifying and evaluating CTCs, as opposed to positive selection approaches, as it is not subjective to a selection bias and can be tailored to accommodate a variety of cytoplasmic and surface markers which can be evaluated to identify a multitude of phenotypic patterns within CTCs from individual patients, including so-called EMT as presented here.
- Subjects :
- Male
Pathology
lcsh:Medicine
Vimentin
medicine.disease_cause
Metastasis
chemistry.chemical_compound
0302 clinical medicine
Circulating tumor cell
Engineering
Basic Cancer Research
Oral Leukoplakia
lcsh:Science
0303 health sciences
Multidisciplinary
Lymphomas of the Head and Neck
biology
Epithelial cell adhesion molecule
Middle Aged
Chemical Engineering
Epithelial Cell Adhesion Molecule
Neoplastic Cells, Circulating
Head and Neck Tumors
Chemistry
Oncology
Head and Neck Neoplasms
030220 oncology & carcinogenesis
Carcinoma, Squamous Cell
Medicine
Female
Cancer Screening
Research Article
Adult
medicine.medical_specialty
Epithelial-Mesenchymal Transition
Bioengineering
03 medical and health sciences
Head and Neck Squamous Cell Carcinoma
Antigens, Neoplasm
Diagnostic Medicine
Cell Line, Tumor
medicine
Biomarkers, Tumor
Cancer Detection and Diagnosis
Early Detection
Humans
Epithelial–mesenchymal transition
Biology
030304 developmental biology
Aged
CD44
lcsh:R
Cancers and Neoplasms
medicine.disease
chemistry
Otorhinolaryngology
Cancer cell
biology.protein
Leukocyte Common Antigens
lcsh:Q
Medicinal Chemistry
Carcinogenesis
Cell Adhesion Molecules
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....f37de9af665ee8c446b716c6899e044d