epithelial-mesenchymal transition during metastasis of hpv-negative pharyngeal squamous cell carcinoma
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2018
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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.
| Reference Key |
ihler2018biomedepithelial-mesenchymal
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|---|---|
| Authors | ;Friedrich Ihler;Ronja Gratz;Hendrik A. Wolff;Bernhard G. Weiss;Mattis Bertlich;Julia Kitz;Gabriela Salinas;Margret Rave-Fränk;Martin Canis |
| Journal | spectrochimica acta - part a: molecular and biomolecular spectroscopy |
| Year | 2018 |
| DOI |
10.1155/2018/7929104
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| URL | |
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