학술논문
Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell Carcinoma.
Document Type
Academic Journal
Author
Ihler F; Department of Otorhinolaryngology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, Germany.; Gratz R; Department of Otorhinolaryngology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, Germany.; Department of Radiotherapy and Radiation Oncology, Pius-Hospital Oldenburg, Georgstrasse 12, 26121 Oldenburg, Germany.; Wolff HA; University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, Germany.; Strahlentherapie Radiologie München, Burgstrasse 7, 80331 München, Germany.; Weiss BG; Department of Otorhinolaryngology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, Germany.; Bertlich M; Department of Otorhinolaryngology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, Germany.; Kitz J; Department of Pathology, University Medical Center Göttingen, Georg-August-University Göttingen, Göttingen, Germany.; Salinas G; Transcriptome and Genome Analysis Laboratory (TAL), Department of Developmental Biochemistry, University Medical Center Göttingen, Georg-August-University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.; Rave-Fränk M; Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, Germany.; Canis M; Department of Otorhinolaryngology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, Germany.
Source
Publisher: Hindawi Pub. Co Country of Publication: United States NLM ID: 101600173 Publication Model: eCollection Cited Medium: Internet ISSN: 2314-6141 (Electronic) NLM ISO Abbreviation: Biomed Res Int Subsets: MEDLINE
Subject
Language
English
Abstract
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.