Overexpression of S100A4 Predicts Migration, Invasion, and Poor Prognosis of Hypopharyngeal Squamous Cell Carcinoma

• Published in: Molecular diagnosis & therapy 2019-06, Vol.23 (3), p.407-417
• Main Authors: Xu, Jianing, Gross, Neil, Zang, Yuanwei, Cao, Shengda, Yang, Feilong, Yang, Zheng, Yu, Wenbin, Lei, Dapeng, Pan, Xinliang
• Format: Article
• Language: English
• Subjects: Antibodies; Apoptosis; Biomarkers; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer; Cancer Research; Cell cycle; Cell migration; Experiments; Gene expression; Human Genetics; Immunohistochemistry; Laboratory Medicine; Lymphatic system; Medical prognosis; Metastases; Metastasis; Molecular Medicine; Original Research Article; Patients; Pharmacotherapy; Phenotypes; Prognosis; Radiation therapy; S100A4 protein; Squamous cell carcinoma; Tumors
• ISSN: 1177-1062; 1179-2000
• DOI: 10.1007/s40291-019-00393-2

Introduction Hypopharyngeal squamous cell carcinoma (HSCC) is among the most lethal tumors encountered in the head and neck and frequently involves regional metastasis. However, the mechanism underlying the aggressiveness of HSCC remains elusive. S100A4 is a well-established metastasis-promoting regulator in a variety of malignancies, but its role in HSCC has not yet been identified. Objectives Our objectives were to explore the expression levels of S100A4 in HSCC tumors and its association with clinicopathological parameters and the clinical prognosis of HSCC and to confirm its role in the metastatic process of the HSCC FaDu cell line in vitro. Methods We assessed the expression levels of S100A4 with immunohistochemistry (IHC) in HSCC tumors ( n  = 71) and adjacent normal tissues ( n  = 44). In vitro experiments were performed to explore the impact of S100A4 knockdown on biological phenotypes of human HSCC FaDu cell line, including migration, invasion, proliferation, apoptosis, and cell cycle. Results The expression of S100A4 was elevated in HSCC tumors compared with adjacent normal tissues and positively correlated with cervical lymph node metastasis in this HSCC patient cohort. In vitro experiments showed that S100A4 knockdown significantly impaired migration and invasion and increased the proportion of cells in G0/G1 phase with no change in proliferation or apoptosis in FaDu cells. Additionally, nuclear S100A4 expression proved to be an independent prognostic indicator in patients with HSCC. Conclusion This study demonstrated for the first time that S100A4 expression is upregulated in HSCC tumors and that this upregulation is positively correlated with cervical lymph node metastasis of this malignancy. The metastasis-promoting role of S100A4 was further validated in the HSCC FaDu cell line, indicating that S100A4 is a potential therapeutic target for HSCC. Furthermore, this study suggests that nuclear S100A4 expression could be considered a prognostic biomarker for HSCC.