Mechanism of endothelial progenitor cell recruitment into neo-vessels in adjacent non-tumor tissues in hepatocellular carcinoma

BMC Cancer

Research Article

Lin-yuan Zhuang¹  Yi-tao Ding²  Chun-ping Jiang²  Xi-tai Sun²  De-cai Yu²  Jun Chen³ 

[1] Institute of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China;Institute of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China;Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China;Institute of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China;Department of Pathology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China;

关键词: Liver Cirrhosis;    Angiogenic Factor;    Endothelial Progenitor Cell;    Cirrhotic Liver;    Intrahepatic Metastasis;   

DOI  :  10.1186/1471-2407-10-435

 received in 2010-02-17, accepted in 2010-08-17,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundWe investigated the distribution and clinical significance of mobilized endothelial progenitor cells (EPCs) in hepatocellular carcinoma (HCC). We found that many more EPCs were recruited to nonmalignant liver tissue (especially into adjacent non-tumor tissues (AT)) than to tumor vessels. These results suggest that the mechanism underlying the recruitment of EPCs into microvessels in AT merits further investigationMethodsAngiogenic factors were detected in three tissue microarrays comprising normal liver, paired tumor tissue (TT) and AT from 105 patients (who had undergone hepatectomy for HCC) using immunohistochemistry. Also, the number of EPCs (positive for Sca-1, Flk-1 and c-Kit) in the blood and liver of cirrhotic mice were determined by flow cytometry and immunohistochemistry. The distribution of these labeled EPCs in tumor and non-tumor tissues was then studied.ResultsThe results from the tissue microarrays showed that the expression levels of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, and endostatin were significantly higher in AT than in either normal liver or TT (p < 0.05), but no significant difference was found in the expression levels of COX-2 and NOS-2 between AT and TT. The expression of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, endostatin, COX-2, and NOS-2 in normal liver tissue was weaker than that in AT or TT. In cirrhotic mice, the number of circulating endothelial progenitor cells gradually increased, before decreasing again. In this mouse model, increased numbers of EPCs were recruited and homed specifically to the cirrhotic liver.ConclusionsBoth liver cirrhosis and HCC led to increased expression of pro-angiogenic factors, which resulted in the recruitment of EPCs into AT. Also, EPCs were mobilized, recruited and homed to cirrhotic liver. The unique pathology of HCC coupled with liver cirrhosis may, therefore, be associated with the distribution and function of EPCs.

【 授权许可】

Unknown   
© Yu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.