Xiao Jian-Bing, Li Xin-Lei, Liu Le, Wang Geng, Hao Song-Nan, Dong Hui-Juan, Wang Xue-Min, Zhang Ya-Fang, Liu Hui-Dong
1Department of Anatomy, Harbin Medical University, 194 Xuefu Road, Harbin, 150081 China.
Department of Orthopedics, Harbin Fifth Hospital, 27 Jiankang Road, Harbin, 150040 China.
Cancer Cell Int. 2018 Jun 22;18:87. doi: 10.1186/s12935-018-0584-1. eCollection 2018.
Semaphorin 5A has been linked to tumor growth, invasion, and metastasis in pancreatic cancer. However, the role of semaphorin 5A in cervical cancer is not known. Our aim is to investigate the prognostic value of semaphorin 5A and its potential role in lymphangiogenesis and invasion in cervical cancer.
In this study, pathological features and clinical data of 232 cervical cancer patients were retrospectively reviewed. Semaphorin 5A protein and mRNA expression was detected by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction, respectively. In vitro, we determined the role and mechanistic pathways of semaphorin 5A in tumor progression in cervical carcinoma cell lines.
Semaphorin 5A expression was significantly higher in stage IIb tumors than in stage Ia, Ib, and IIa tumors. High semaphorin 5A expression was significantly associated with pelvic lymph node metastasis, lymphovascular permeation, and poor survival. Semaphorin 5A induced lymphangiogenesis through a plexin-B/Met/vascular endothelial growth factor-C pathway. Semaphorin 5A also increased cervical cancer cell invasion by stimulating the expression and activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 via PI3K/AKT and plexin-B3.
Our findings indicate that semaphorin 5A may represent a poor prognostic biomarker and anti-metastasis therapeutic target in cervical cancer.
信号素5A已被证实与胰腺癌的肿瘤生长、侵袭和转移有关。然而，信号素5A在宫颈癌中的作用尚不清楚。我们的目的是研究信号素5A在宫颈癌中的预后价值及其在淋巴管生成和侵袭中的潜在作用。
在本研究中，回顾性分析了232例宫颈癌患者的病理特征和临床资料。分别采用免疫组织化学和定量实时逆转录-聚合酶链反应检测信号素5A蛋白和mRNA表达。在体外，我们确定了信号素5A在宫颈癌细胞系肿瘤进展中的作用和机制途径。
信号素5A在IIb期肿瘤中的表达明显高于Ia、Ib和IIa期肿瘤。信号素5A高表达与盆腔淋巴结转移、淋巴管浸润及预后不良显著相关。信号素5A通过丛状蛋白-B/Met/血管内皮生长因子-C途径诱导淋巴管生成。信号素5A还通过PI3K/AKT和丛状蛋白-B3刺激基质金属蛋白酶-2和基质金属蛋白酶-9的表达和活性，增加宫颈癌细胞的侵袭。
我们的研究结果表明，信号素5A可能是宫颈癌预后不良的生物标志物和抗转移治疗靶点。
