NHC Key Laboratory of Otorhinolaryngology, Department of Otorhinolaryngology, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, China.
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Mol Diagn Ther. 2019 Jun;23(3):407-417. doi: 10.1007/s40291-019-00393-2.
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.
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.
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.
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.
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.
下咽鳞状细胞癌（HSCC）是头颈部最致命的肿瘤之一，常伴有区域转移。然而，HSCC 侵袭性的机制仍不清楚。S100A4 是多种恶性肿瘤中一种成熟的促进转移的调节因子，但它在 HSCC 中的作用尚未确定。
本研究旨在探讨 S100A4 在 HSCC 肿瘤中的表达水平及其与临床病理参数的关系和 HSCC 的临床预后，并在体外确认其在 HSCC FaDu 细胞系转移过程中的作用。
我们采用免疫组织化学（IHC）方法评估了 71 例 HSCC 肿瘤和 44 例相邻正常组织中 S100A4 的表达水平。体外实验探讨了 S100A4 敲低对人 HSCC FaDu 细胞系生物学表型的影响，包括迁移、侵袭、增殖、凋亡和细胞周期。
与相邻正常组织相比，S100A4 在 HSCC 肿瘤中的表达升高，并且在该 HSCC 患者队列中与颈部淋巴结转移呈正相关。体外实验表明，S100A4 敲低显著抑制了 FaDu 细胞的迁移和侵袭，并增加了 G0/G1 期细胞的比例，而对增殖或凋亡没有影响。此外，核 S100A4 表达被证明是 HSCC 患者的独立预后指标。
本研究首次证明 S100A4 在 HSCC 肿瘤中表达上调，且这种上调与该恶性肿瘤的颈部淋巴结转移呈正相关。S100A4 在 HSCC FaDu 细胞系中的促转移作用进一步得到验证，表明 S100A4 可能是 HSCC 的一个潜在治疗靶点。此外，本研究表明核 S100A4 表达可作为 HSCC 的预后生物标志物。
