Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell Carcinoma
In epithelial tumors, a shift towards a mesenchymal phenotype has been associated with increased invasiveness and metastasis. It is assumed that this phenomenon plays a major role in disease progression and ultimately prognosis. This study investigated epithelial-mesenchymal transition (EMT) in huma...
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doaj-1e0b4d1fec4e40ddb945da2eccbbf0042020-11-24T22:38:49ZengHindawi LimitedBioMed Research International2314-61332314-61412018-01-01201810.1155/2018/79291047929104Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell CarcinomaFriedrich Ihler0Ronja Gratz1Hendrik A. Wolff2Bernhard G. Weiss3Mattis Bertlich4Julia Kitz5Gabriela Salinas6Margret Rave-Fränk7Martin Canis8Department of Otorhinolaryngology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, GermanyDepartment of Otorhinolaryngology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, GermanyUniversity Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, GermanyDepartment of Otorhinolaryngology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, GermanyDepartment of Otorhinolaryngology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, GermanyDepartment of Pathology, University Medical Center Göttingen, Georg-August-University Göttingen, Göttingen, GermanyTranscriptome and Genome Analysis Laboratory (TAL), Department of Developmental Biochemistry, University Medical Center Göttingen, Georg-August-University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, GermanyDepartment of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, GermanyDepartment of Otorhinolaryngology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, GermanyIn epithelial tumors, a shift towards a mesenchymal phenotype has been associated with increased invasiveness and metastasis. It is assumed that this phenomenon plays a major role in disease progression and ultimately prognosis. This study investigated epithelial-mesenchymal transition (EMT) in human papillomavirus- (HPV-) negative pharyngeal squamous cell carcinoma. Tissue was obtained from one hypopharyngeal primary tumor and a regional lymph node metastasis during surgery with curative intention. A cell culture was established from the primary tumor and mesenchymal growth conditions were emulated. Gene expression profiling was performed (Human 8 × 60 K design array, Agilent Technologies) and EMT was assessed by a gene set (MSigDB: M5930, Hallmark_epithelial_mesenchymal_transition), applying gene set expression analysis (GSEA). Immunohistochemical staining and flow cytometry of CD44 and E-cadherin were compared in primary tumor, metastasis, and cell cultures. Primary tumor and metastasis were highly positive for CD44. A loss of E-cadherin occurred in the metastasis. Flow cytometry showed the appearance of a population without E-cadherin in spheroid colonies. In GSEA, the EMT phenotype was enriched in the primary tumor compared to metastasis and cell cultures (FDR < 25%, p < 5%). EMT showed variable expression during metastasis. It may thereby be a dynamic state in HPV-negative pharyngeal squamous cell carcinoma that is active only during the process of metastasis itself. Thereby, the primary tumor as well as the metastasis may exhibit fewer EMT properties.http://dx.doi.org/10.1155/2018/7929104 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Friedrich Ihler Ronja Gratz Hendrik A. Wolff Bernhard G. Weiss Mattis Bertlich Julia Kitz Gabriela Salinas Margret Rave-Fränk Martin Canis |
spellingShingle |
Friedrich Ihler Ronja Gratz Hendrik A. Wolff Bernhard G. Weiss Mattis Bertlich Julia Kitz Gabriela Salinas Margret Rave-Fränk Martin Canis Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell Carcinoma BioMed Research International |
author_facet |
Friedrich Ihler Ronja Gratz Hendrik A. Wolff Bernhard G. Weiss Mattis Bertlich Julia Kitz Gabriela Salinas Margret Rave-Fränk Martin Canis |
author_sort |
Friedrich Ihler |
title |
Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell Carcinoma |
title_short |
Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell Carcinoma |
title_full |
Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell Carcinoma |
title_fullStr |
Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell Carcinoma |
title_full_unstemmed |
Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell Carcinoma |
title_sort |
epithelial-mesenchymal transition during metastasis of hpv-negative pharyngeal squamous cell carcinoma |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2018-01-01 |
description |
In epithelial tumors, a shift towards a mesenchymal phenotype has been associated with increased invasiveness and metastasis. It is assumed that this phenomenon plays a major role in disease progression and ultimately prognosis. This study investigated epithelial-mesenchymal transition (EMT) in human papillomavirus- (HPV-) negative pharyngeal squamous cell carcinoma. Tissue was obtained from one hypopharyngeal primary tumor and a regional lymph node metastasis during surgery with curative intention. A cell culture was established from the primary tumor and mesenchymal growth conditions were emulated. Gene expression profiling was performed (Human 8 × 60 K design array, Agilent Technologies) and EMT was assessed by a gene set (MSigDB: M5930, Hallmark_epithelial_mesenchymal_transition), applying gene set expression analysis (GSEA). Immunohistochemical staining and flow cytometry of CD44 and E-cadherin were compared in primary tumor, metastasis, and cell cultures. Primary tumor and metastasis were highly positive for CD44. A loss of E-cadherin occurred in the metastasis. Flow cytometry showed the appearance of a population without E-cadherin in spheroid colonies. In GSEA, the EMT phenotype was enriched in the primary tumor compared to metastasis and cell cultures (FDR < 25%, p < 5%). EMT showed variable expression during metastasis. It may thereby be a dynamic state in HPV-negative pharyngeal squamous cell carcinoma that is active only during the process of metastasis itself. Thereby, the primary tumor as well as the metastasis may exhibit fewer EMT properties. |
url |
http://dx.doi.org/10.1155/2018/7929104 |
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