Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Oncology, The Second Affiliated Hospital of AnHui Medical University, Hefei, China.
Biochem Biophys Res Commun. 2020 Apr 16;524(4):1064-1071. doi: 10.1016/j.bbrc.2020.02.042. Epub 2020 Feb 15.
Tumor associated macrophages (TAMs) promoted pancreatic ductal adenocarcinoma (PDAC) initiation and progression. In this study we aimed to evaluate CD10 expression by monocytes/macrophages and its clinical significance in PDAC.
Human CD14 peripheral blood monocytes were isolated and cultured for 6-7 days to differentiate into macrophages in vitro. Monocytic THP-1 cells were cultured and treated with 100 ng/ml phorbol 12-myristate 13-acetate (PMA) for 72 h to induce macrophage differentiation. Reverse transcription-quantitative PCR, immunohistochemistry, immunofluorescence, multiplex immunohistochemical staining and flow cytometry were performed to detect CD10 expression. In addition, the correlations between CD10 expression and immune cells infiltration were investigated through TIMER or GEPIA. Finally, Kaplan-Meier plotter and GEPIA databases were adopted to evaluate the influence of CD10 on clinical prognosis.
Our results indicated that CD10 was expressed by a subset of human monocytes and many more cells expressed CD10 after differentiation into macrophages in vitro (13.19% vs. 41.39%; P < 0.0001). As for PDAC tissues, CD10 was correlated with immune cells infiltration and was expressed by a subset of TAMs. For THP-1 cells, PMA could induce CD10 expression through the MAPK pathway. The Kaplan-Meier plotter results suggested that CD10 expression had an impact on the prognosis of PDAC.
In this study we demonstrated that CD10 was expressed by human primary monocytes, human monocyte-derived macrophages and TAMs, and was correlated with poor prognosis in PDAC, suggesting CD10 to be a potential therapeutic target in PDAC.
肿瘤相关巨噬细胞(TAMs)促进了胰腺导管腺癌(PDAC)的发生和发展。本研究旨在评估单核细胞/巨噬细胞中 CD10 的表达及其在 PDAC 中的临床意义。
分离人外周血 CD14 单核细胞并在体外培养 6-7 天分化为巨噬细胞。培养单核细胞 THP-1 细胞并用 100ng/ml 佛波醇 12-肉豆蔻酸 13-乙酸酯(PMA)处理 72 小时诱导巨噬细胞分化。采用逆转录定量 PCR、免疫组织化学、免疫荧光、多重免疫组织化学染色和流式细胞术检测 CD10 的表达。此外,通过 TIMER 或 GEPIA 研究 CD10 表达与免疫细胞浸润的相关性。最后,采用 Kaplan-Meier 绘图器和 GEPIA 数据库评估 CD10 对临床预后的影响。
我们的结果表明,CD10 由人类单核细胞中的一个亚群表达,在体外分化为巨噬细胞后更多的细胞表达 CD10(13.19% vs. 41.39%;P<0.0001)。对于 PDAC 组织,CD10 与免疫细胞浸润相关,并由 TAMs 的一个亚群表达。对于 THP-1 细胞,PMA 可以通过 MAPK 途径诱导 CD10 表达。Kaplan-Meier 绘图器结果表明,CD10 表达对 PDAC 的预后有影响。
本研究表明,CD10 由人原代单核细胞、人单核细胞衍生的巨噬细胞和 TAMs 表达,并与 PDAC 的不良预后相关,提示 CD10 可能成为 PDAC 的潜在治疗靶点。