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E-选择素及其配体对肝细胞癌黏附转移的影响

[Effects of E-selectin and their ligands on the adhesive metastasis of hepatocellular carcinoma].

作者信息

Qian Shi-Kun, Chen De, Li Yue, Yang Xue-Wei, Deng Wu-Jian, Li Qiang, Lin Hang, Hu Hai, Xiao Jun-Qi, Chen Song-Wei

机构信息

Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2010 Jun;18(6):440-4. doi: 10.3760/cma.j.issn.1007-3418.2010.06.011.

Abstract

OBJECTIVES

To explore the effects of E-selectin, ICAM-1 and their ligands on the adhesive metastasis of hepatocellular carcinoma (HCC), and to select possible anti-adhesion drugs for hepatocellular carcinoma metastasis.

METHODS

78 HCC patients were analyzed with the correlation of clinical features to the expression levels of E-selectin, sLeX, sLeA and CD44v6 in the tumor tissue. The adhesion between HepG2 and endothelial cell lines was examined by solid phase adhesion assay in vitro. Two kinds of drugs were accessed for their anti-adhesion ability.

RESULTS

The positive rate of E-selectin in vascular endothelia cells adjacent to cancer nest is 70.51%, and which of sLeX, sLeA, CD44v6 within tumor cells is 64.10%, 69.23%, 62.90% respectively. The patients' life span is closely related with the positive expression of sLeX, sLeA, CD44v6 (P = 0.008, 0.001, 0.022). The positive expression of E-selectin, sLeX and sLeA is significantly correlated to portal vein tumor thrombus (PVTT), preoperative extrahepatic metastasis, and satellite foci, but not to the size of tumor and AFP. The level of CD44v6 expression is significantly correlated to patient's survival time. The expression levels of E-selectin and ICAM-1 are remarkably higher after ED25 and ECV304 cell lines be activated. Meanwhile the adhesive ability of HepG2 to endothelial cell is mediated. Dexamethasone, tanshinone IIA are able to block this adhesion at low concentration.

CONCLUSION

The expression levels of E-selectin, sLeX, sLeA and CD44v6 are closely correlated with clinical features. E-selectin, ICAM-1 and their ligands are important molecules of hepatocellular carcinoma and endothelial cells to tumor adhesive metastasis. Dexamethasone, tanshinone II A can be hopefully used as anti-adhesion drugs.

摘要

目的

探讨E-选择素、细胞间黏附分子-1(ICAM-1)及其配体对肝细胞癌(HCC)黏附转移的影响,并筛选可能用于肝癌转移的抗黏附药物。

方法

分析78例HCC患者的临床特征与肿瘤组织中E-选择素、唾液酸化路易斯寡糖X(sLeX)、唾液酸化路易斯寡糖A(sLeA)和CD44v6表达水平的相关性。采用体外固相黏附试验检测HepG2细胞与内皮细胞系之间的黏附情况。评估两种药物的抗黏附能力。

结果

癌巢旁血管内皮细胞中E-选择素的阳性率为70.51%,肿瘤细胞中sLeX、sLeA、CD44v6的阳性率分别为64.10%、69.23%、62.90%。患者的生存期与sLeX、sLeA、CD44v6的阳性表达密切相关(P = 0.008、0.001、0.022)。E-选择素、sLeX和sLeA的阳性表达与门静脉癌栓(PVTT)、术前肝外转移及卫星灶显著相关,但与肿瘤大小和甲胎蛋白无关。CD44v6的表达水平与患者的生存时间显著相关。ED25和ECV304细胞系激活后,E-选择素和ICAM-1的表达水平显著升高。同时介导了HepG2与内皮细胞的黏附能力。地塞米松、丹参酮IIA在低浓度时能够阻断这种黏附。

结论

E-选择素、sLeX、sLeA和CD44v6的表达水平与临床特征密切相关。E-选择素、ICAM-1及其配体是肝癌细胞与内皮细胞发生肿瘤黏附转移的重要分子。地塞米松、丹参酮IIA有望用作抗黏附药物。

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