Yu De-Cai, Chen Jun, Ding Yi-Tao
Institute of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China; E-Mail:
Int J Mol Sci. 2010 Aug 9;11(8):2901-9. doi: 10.3390/ijms11082901.
Our previous investigations showed that mobilized endothelial progenitor cells (EPCs) are enriched in non-tumor tissues (NT) surrounding hepatocellular carcinoma (HCC), compared to in tumor tissues (TT). This particular recruitment of EPCs is worth investigating further. The mobilization, recruitment, homing, and incorporation of EPCs into tumors require the participation of multiple factors, including angiogenic factors, adherent molecules, endothelial cells, hypoxic environment, etc. Therefore, we hypothesized that NT might be a hypoxic and highly angiogenic area, into which many more EPCs are recruited and homed. In the last three years, we evaluated the hypoxic condition, angiogenic factors and angiogenic index using frozen tissues or tissue microarrays from 105 patients who had undergone hepatectomy for HCC, and here we review our results and the studies of others. All results showed the expression of Hypoxiainducible factor-1α was higher in NT than in TT. The expression of VEGFA, bFGF, TGF-β, MCP-1, MMP-9, TIMP-2, and endostatin in NT was significantly higher than in normal liver and TT. Meanwhile, the expression of CD105-the surface marker of activated endothelial cells-was also higher in NT than in TT at the protein and mRNA levels. These investigations showed that NT is a hypoxic and highly angiogenic area, which may be the 'niche' of EPCs. The particular background in HCC may be related to liver cirrhosis. Therefore, non-tumor tissues surrounding HCC may be the 'niche' of endothelial progenitor cells.
我们之前的研究表明，与肿瘤组织（TT）相比，动员的内皮祖细胞（EPCs）在肝细胞癌（HCC）周围的非肿瘤组织（NT）中更为富集。EPCs的这种特殊募集值得进一步研究。EPCs向肿瘤的动员、募集、归巢及整合需要多种因素的参与，包括血管生成因子、黏附分子、内皮细胞、缺氧环境等。因此，我们推测NT可能是一个缺氧且血管生成高度活跃的区域，会募集并归巢更多的EPCs。在过去三年中，我们使用105例接受肝癌肝切除术患者的冷冻组织或组织芯片评估了缺氧状况、血管生成因子及血管生成指数，在此我们回顾我们的研究结果以及其他研究的结果。所有结果均显示，缺氧诱导因子-1α在NT中的表达高于TT。NT中血管内皮生长因子A（VEGFA）、碱性成纤维细胞生长因子（bFGF）、转化生长因子-β（TGF-β）、单核细胞趋化蛋白-1（MCP-1）、基质金属蛋白酶-9（MMP-9）、金属蛋白酶组织抑制因子-2（TIMP-2）和内皮抑素的表达显著高于正常肝脏和TT。同时，活化内皮细胞的表面标志物CD105在NT中的蛋白质和mRNA水平表达也高于TT。这些研究表明，NT是一个缺氧且血管生成高度活跃的区域，可能是EPCs的“生态位”。HCC的特殊背景可能与肝硬化有关。因此，HCC周围的非肿瘤组织可能是内皮祖细胞的“生态位”。
