癌症患者来源的循环微粒在大鼠模型中增强肺转移：双源CT、细胞和分子研究

Cancer Patient-Derived Circulating Microparticles Enhance Lung Metastasis in a Rat Model: Dual-Source CT, Cellular, and Molecular Studies.

作者信息

Ko Sheung-Fat, Yip Hon-Kan, Zhen Yen-Yi, Lee Chia-Chang, Li Jung-Hui, Lee Chen-Chang, Leu Steve, Huang Chung-Cheng, Ng Shu-Hang, Lin Jui-Wei

机构信息

Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung, 833, Taiwan.

Department of Cardiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan.

出版信息

Mol Imaging Biol. 2016 Aug;18(4):490-9. doi: 10.1007/s11307-015-0923-8.

DOI:10.1007/s11307-015-0923-8

PMID:26669780

Abstract

PURPOSE

This study aimed to test the hypothesis that lung cancer patient-derived circulating microparticles (LCC-MPs) enhance metastatic lung tumors in a rat model.

PROCEDURES

The controls (n = 6) and LCC-MP-treated rats (n = 6) with N1S1-induced pulmonary metastatic hepatocellular carcinoma (HCC) underwent dual-source CT (DSCT) on days 10, 15, and 20. Cellular and molecular studies were performed subsequently.

RESULTS

DSCT revealed slow progression of metastatic lung tumors in the controls. Compared with the controls, the LCC-MP-treated rats exhibited significantly more and larger metastatic tumors on days 15 and 20 on DSCT, enhanced angiogenesis with higher microvessel count (CD34+), more CXCR4+ and VEGF+ cells in immunohistofluorescence studies, and higher protein expression levels of eNOS, angiopoietin, vascular endothelial growth factor, and CD31 on western blotting (Mann-Whitney test, all P < 0.05).

CONCLUSIONS

LCC-MPs can elicit oncogenic stimulation and accelerate metastatic HCC growth in rat lung as demonstrated on DSCT and enhanced tumoral angiogenesis as confirmed in cellular and molecular studies.

摘要

目的

本研究旨在验证肺癌患者来源的循环微粒（LCC-MPs）在大鼠模型中增强转移性肺肿瘤的这一假设。

程序

对对照组（n = 6）和经LCC-MPs处理的大鼠（n = 6），其通过N1S1诱导产生肺转移性肝细胞癌（HCC），分别在第10、15和20天进行双源CT（DSCT）检查。随后进行细胞和分子研究。

结果

DSCT显示对照组中转移性肺肿瘤进展缓慢。与对照组相比，经LCC-MPs处理的大鼠在DSCT检查的第15天和第20天出现了明显更多、更大的转移性肿瘤，免疫组织荧光研究显示微血管生成增强，微血管计数（CD34+）更高，CXCR4+和VEGF+细胞更多，蛋白质印迹法显示内皮型一氧化氮合酶、血管生成素、血管内皮生长因子和CD31的蛋白质表达水平更高（曼-惠特尼检验，所有P < 0.05）。