骨髓细胞参与肝癌新生血管的构建-东南大学学报医学版

骨髓细胞参与肝癌新生血管的构建

单位：1. 南京医科大学第一附属医院肿瘤科, 江苏南京 210029;
2. 江苏省肿瘤医院/南京医科大学附属肿瘤医院/江苏省肿瘤研究所普外科, 江苏南京 210009;
3. 南京医科大学第一附属医院检验学部, 江苏南京 210029

分类号：R735.7

出版年·卷·期（页码）：2018·37·第五期（841-845）

摘要：

目的：探讨骨髓干细胞（BMSCs）是否参与肝癌血管新生。方法：采用骨髓移植技术（GFP）建立标记骨髓的小鼠肝癌模型。ELISA测定血清血管内皮生长因子（VEGF）的浓度；流式细胞术测定循环BMSCs含量；GFP示踪BMSCs在肝癌组织中的分布；免疫荧光方法观察BMSCs是否参与肝癌血管新生过程；蛋白印迹法观察无瘤区和肿瘤区VEGF表达的差异。结果：荧光镜下显示GFP⁺骨髓的小鼠肝癌模型中大量BMSCs富集于肝癌组织中，肝癌小鼠血清VEGF浓度为（175.13±52.34）pg·ml^-1，显著高于对照组的（81.65±32.71）pg·ml^-1（P<0.05）；同时循环CD133⁺CD34⁺和CD133⁺VEGFR2⁺细胞明显增多，分别为（0.27±0.13）%和（0.16±0.08）%，显著高于对照组的（0.07±0.04）%和（0.08±0.06）%（P<0.01）。免疫荧光结果提示BMSCs动员后在肿瘤区富集并且参与肝癌新生血管的构建，并且BMSCs在肝癌新生血管中的比例从7.6%（建模7 d）逐渐升高到19.3%（建模14 d）（P<0.05）。结论：BMSCs参与肝癌新生血管的构建。

Objective:To explore whether or not bone marrow stem cells (BMSCs) participate the angiogenesis in hepatocellular carcinoma (HCC). Methods:Bone marrow-GFP⁺ orthotropic hepatic caner mice were built by bone marrow transplantation. The change of circulating BMSCs and serum vascular endothelial growth factor (VEGF) in HCC mice were measured by flow cytometry and ELISA. Intrahepatic distribution of BMSCs was evaluated using immunofluorescent. Western blotting was performed to examine the expression of VEGF in tumor tissues and tumor free tissues. Results:Compared with controls, the level of serum VEGF of HCC mice was much higher[(175.13±52.34) pg·ml^-1 vs (81.65±32.71) pg·ml^-1,P<0.05].The frequency of circulating CD133⁺CD34⁺ and CD133⁺ VEGFR2⁺ BMSCs of HCC mice was increased significantly relative to control group[(0.27±0.13)% and (0.16±0.08)% vs (0.07±0.04)% and (0.08±0.06)%,P<0.01]. BMSCs had been mobilized, recruited into tumor and incorporated into hepatic new vessels. With tumor growth, the proportion of BMCs in vessels increased gradually from 7.6% at 7 d to 19.3% at 14 d after HCC building. Conclusion:BMSCs participate the angiogenesis of HCC.

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