Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell Carcinoma

• Published in: BioMed research international 2018-01, Vol.2018 (2018), p.1-12
• Main Authors: Canis, Martin, Rave-Fränk, Margret, Kitz, Julia, Bertlich, Mattis, Weiss, Bernhard, Wolff, Hendrik A., Gratz, Ronja, Ihler, Friedrich, Salinas, Gabriela
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Biomarkers, Tumor - metabolism; Biotechnology; Cadherins - metabolism; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; CD44 antigen; Cell culture; Cell Line, Tumor; Chemotherapy; Cytometry; Development and progression; E-cadherin; Epithelial-Mesenchymal Transition - physiology; Flow cytometry; Gene expression; Genotype & phenotype; Growth conditions; Head & neck cancer; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Human papillomavirus; Human performance; Humans; Hyaluronan Receptors - metabolism; Immunohistochemistry; Immunotherapy; Instrument industry; Invasiveness; Lymph nodes; Male; Medical research; Mesenchyme; Metastases; Metastasis; Middle Aged; Motivation; Neoplasm Metastasis - pathology; Papillomaviridae - pathogenicity; Papillomavirus infections; Pharyngeal Neoplasms - metabolism; Pharyngeal Neoplasms - pathology; Pharynx; Phenotypes; Prognosis; Proteomics; Signal transduction; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Stem cells; Surgery; Throat cancer; Tumors
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2018/7929104

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.