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CD110 促进胰腺癌进展,其表达与不良预后相关。

CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis.

机构信息

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan.

Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

J Cancer Res Clin Oncol. 2019 May;145(5):1147-1164. doi: 10.1007/s00432-019-02860-z. Epub 2019 Feb 15.

Abstract

PURPOSE

This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer.

METHODS

We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin-CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model.

RESULTS

CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK-MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model.

CONCLUSIONS

CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.

摘要

目的

本研究旨在探讨 CD110 表达在胰腺癌中的功能和意义。

方法

我们对 86 例胰腺癌患者的肿瘤样本进行了 CD110 表达的免疫组织化学染色。我们评估了临床结果和其他临床病理因素,以确定 CD110 对生存和肝转移的意义。我们在体外和体内研究了血小板生成素-CD110 信号在癌细胞外渗中的作用。我们研究了在脾异种移植小鼠模型中敲低 CD110 对肝转移的影响。

结果

癌细胞中 CD110 的表达与低组织学分级的浸润性导管癌相关,高 CD110 表达的患者预后较差(P = 0.0003)。高 CD110 表达是肝转移的独立预测因子(P = 0.0422)。敲低 CD110 表达显著减弱了细胞迁移和侵袭。血小板生成素的处理促进了胰腺癌细胞的外渗。在血小板生成素存在的情况下,CD110 通过激活 ERK-MYC 信号通路增加了细胞活力。敲低 CD110 表达抑制了小鼠模型中的肝转移。

结论

CD110 促进了胰腺癌的进展,它可能是肝转移的预测因子。

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