CD147 promotes invasion and MMP-9 expression through MEK signaling and predicts poor prognosis in hypopharyngeal squamous cell carcinoma
CD147 promotes invasion and MMP-9 expression through MEK signaling and predicts poor prognosis in hypopharyngeal squamous cell carcinoma
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DOI：
10.17219/acem/128228
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发表时间：
2021-01-01
影响因子：
2.1
通讯作者：
Yamada, Takechiyo
中科院分区：
文献类型：
--
作者：
Suzuki, Shinsuke;Toyoma, Satoshi;Yamada, Takechiyo
背景资料。下咽癌是头颈部最常见的癌症之一，由于复发和转移，预后较差。因此，有必要改善预后，这需要确定预后因素和阐明参与肿瘤进展的机制。越来越多的证据表明，分化簇147(CD147)在包括头颈部鳞状细胞癌(HNSCC)在内的恶性肿瘤中强烈表达，并参与肿瘤的进展。研究CD147在HNSCC细胞中的信号转导途径，探讨CD147介导的肿瘤进展机制，以及CD147在肿瘤中的表达与下咽癌患者生存率的关系。为探讨CD147在HNSCC中的下游信号转导作用，采用酶联免疫吸附试验(LISA)检测CD147配体亲环素A作用下的下咽癌细胞株FaDu中AKT1、MEK1、p38MAPK、STAT3和核因子-kappaB的表达水平。我们发现表达CD147的下咽癌患者的5年总生存率(OS)为11.1%，低于不表达CD147的患者(43.0%)(P=0.02)。我们证实，在下咽癌细胞中，磷酸化的MEK和基质金属蛋白酶-9(MMP9)的表达以及细胞侵袭能力都增强了。此外，CD147诱导的细胞浸润增加和基质金属蛋白酶-9表达增强可被MEK抑制剂阻断。这些结果表明，CD147可以预测预后不良，CD147诱导的MEK介导的细胞内信号通路在下咽癌的肿瘤进展中起着至关重要的作用。
Background. Hypopharyngeal cancer is one of the most frequent head and neck cancers and is associated with a poor prognosis because of recurrence and metastases. Therefore, there is a need to improve the prognosis, which requires the identification of prognostic factors and elucidation of the mechanisms involved in tumor progression. Accumulated evidence has demonstrated that cluster of differentiation 147 (CD147) is strongly expressed in malignant tumors, including head and neck squamous cell carcinoma (HNSCC), and contributes to tumor progression.Objectives. To investigate CD147-induced signaling pathways in HNSCC cells to evaluate the mechanisms of tumor progression mediated by CD147, and the association between CD147 expression in tumors and the survival rate of hypopharyngeal cancer patients.Material and methods. To determine the downstream signaling of CD147 in HNSCC, expression levels of phosphorylated AKT1, MEK1, p38 MAPK, STAT3, and NF-kappa B were evaluated using enzyme-linked immunosorbent assay (LISA) in FaDu, a hypopharyngeal cell line, exposed to cyclophilin A, a CD147 ligand.Results. We found that hypopharyngeal cancer patients expressing CD147 showed a poor five-yea r overall survival (OS) of 11.1% compared with those without CD147 expression (43.0%) (p = 0.02). We confirmed that the expression of phosphorylated MEK and matrix metalloproteinase-9 (MMP-9), as well as cell invasion ability, were enhanced in hypopharyngeal cancer cells. In addition, this increased cell infiltration and enhancement of MMP-9 expression induced by CD147 were abolished by a MEK inhibitor.Conclusions. These results suggest that CD147 can be a predictor of a poor prognosis, and that a CD147-induced MEK-mediated intracellular signaling pathway plays a crucial role in tumor progression in hypopharyngeal carcinoma.