Molecular Mechanism of Recurrence and Metastasis of Primary Hepatocellular Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

MU Siqing , ZHANG Feng

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University， Nanjing 210029, China;

Corresponding author：

Keywords：

Hepatocellular carcinoma; Metastasis; Recurrence; Cytobiology; Molecular biology

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Objective 　The currently pertinent articles about the molecular mechanism of recurrence and metastasis of primary hepatocellular carcinoma (HCC) were reviewed.
Methods 　Literatures that related to the molecular mechanism of the recurrence and metastasis of HCC were summarized retrospectively in this review.
Results 　Several genes, such as the growth factors and the corresponding receptors, the adhesive molecule, and the extracellular matrix and many factors, such as the oxygen supply, tumor angiogenesis and the immune system, all took important roles in the process of recurrence and metastasis of HCC, which involves many steps.
Conclusion 　The study of the recurrence and metastasis of HCC should be emphasized further since early intervening the genes that are related to the recurrence and metastasis may help prevent the recurrence and metastasis of HCC completely, decrease the death rate and improve patients’ life quality in the long term.

Citation： MU Siqing,ZHANG Feng. Molecular Mechanism of Recurrence and Metastasis of Primary Hepatocellular Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(1): 49-52. doi: Copy

1.	褚忠华, 闵军, 凌云彪, 等. 多种黏附分子基因在原发性肝癌的表达及其临床意义 [J]. 中国病理生理杂志， 2004； 20(9)∶1672.
2.	王艳红，刘银坤，李文昌, 等. 抗黏附多肽对人肝癌高转移细胞系MHCC97侵袭转移的抑制作用 [J]. 中华实验外科杂志， 2004； 21（10）∶1168.
3.	王辉, 韩亮, 李庆友. E-钙粘素和γ-连环素与原发性肝癌侵袭转移的关系 [J]. 腹部外科， 2004； 17（6）∶370.
4.	Inayoshi J, Ichida T, Sugitani S, et al. Gross appearance of hepatocellular carcinoma reflects E-cadherin expression and risk of early recurrence after surgical treatment [J]. J Gastroenterol Hepatol, 2003; 18(6)∶673.
5.	陈晚平, 易继林, 李兴睿, 等. 肝细胞性肝癌中E-cadherin和nm23-h1的表达与转移的关系 [J]. 临床外科杂志， 2004； 12（11）∶673.
6.	路艳艳, 周柔丽. 整合素α6β1增强人肝癌细胞侵袭性机制的探讨 [J]. 中华肿瘤杂志， 2000； 22(4)∶287.
7.	Tsuchiya Y, Sawada S, Tsukada K, et al. A new pseudo-peptide of Arg-Gly-Asp (RGD) inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma [J]. Int J Oncol, 2002; 20(2)∶319.
8.	Zhou GF, Ye F, Cao LH, et al. Over expression of integrin alpha 5 beta 1 in human hepatocellular carcinoma cell line suppresses cell proliferation in vitro and tumorigenicity in nude mice [J]. Mol Cell Biochem, 2000; 207(1-2)∶49.
9.	魏民, 曾宪录. 选择素与肿瘤转移 [J]. 生物化学与生物物理进展, 2003; 30(2)∶185.
10.	唐南洪，陈燕凌，李秀金，等. sICAM-1、 sE-selectin水平在肝癌诊疗中的价值 [J]. 中国免疫学杂志， 2001； 17（12）∶671.
11.	Zhang BH, Chen H, Yao XP, et al. E-selectin and its ligand-sLeX in the metastasis of hepatocellular carcinoma [J]. Hepatobiliary Pancreat Dis Int, 2002; 1(1)∶80.
12.	刘剑勇, 张力图, 张春艳, 等. 血浆可溶性P-选择素在原发性肝癌患者中的临床意义 [J]. 临床肝胆病杂志, 2003; 19（1）∶54.
13.	Borsig L, Wong R, Hynes RO, et al.Synergistic effects of L-and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis [J]. Proc Natl Acad Sci USA, 2002; 99(4)∶2193.
14.	孟召伟, 方佩华. 细胞间黏附分子-1临床应用的研究进展 [J]. 天津医药， 2004； 32（11）∶714.
15.	Xu J, Mei MH, Zeng SE, et al. Expressions of ICAM-1 and its mRNA in sera and tissues of patients with hepatocellular carcinoma [J]. World J Gastroenterol, 2001; 7(1)∶120.
16.	彭利, 　王顺祥, 　张风瑞, 等. 基质金属蛋白酶-9和血管内皮生长因子与原发性肝癌侵袭转移关系研究 [J]. 中华肝胆外科杂志， 2003； 9（1）∶42.
17.	Theret N, Musso O, Turlin B, et al. Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas [J]. Hepatology, 2001; 34(1)∶82.
18.	McKenna GJ, Chen Y, Smith RM, et al. A role for matrix metalloproteinases and tumor host interaction in hepatocellular carcinomas [J]. Am J Surg, 2002; 183(5)∶588.
19.	田波, 李雁, 冀学宁, 等. 全反式维甲酸对人肝癌高转移细胞株MHCC97-H表达基质金属蛋白酶的影响 [J]. 中华实验外科杂志， 2003; 20（10）∶900.
20.	Aebersold DM, Burri P, Beer KT, et al. Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer [J]. Cancer Res, 2001; 61(7)∶2911.
21.	Poon RT, Ng IO, Lau C, et al. Serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: a prospective study [J]. Ann Surg, 2001; 233(2)∶227.
22.	刘智敏，严律南，汤宇，等. 血管内皮生长因子和基质金属蛋白酶-9在肝细胞癌中的表达及其意义 [J]. 中国普外基础与临床杂志， 2002; 9(6)∶421.
23.	张明威，王欣，张静，等. 肝细胞肝癌中血管内皮生长因子与浸润树突状细胞表达的相关性研究 [J]. 临床肝胆病杂志， 2005； 21(5)∶288.
24.	Ng IO, Poon RT, Lee JM, et al. Microvessel density, vascular endothelial growth factor and its receptors Flt-1 and Flk-1/KDR in hepatocellular carcinoma [J].Am J Clin Pathol, 2001; 116(6)∶838.
25.	Yao DF, Wu XH, Zhu Y, et al. Quantitative analysis of vascular endothelial growth factor, microvascular density and their clinicopathologic features in human hepatocellular carcinoma [J]. Hepatobiliary Pancreat Dis Int, 2005; 4(2)∶220.
26.	樊利芳，刁路明, 陈德基. 缺氧诱导因子-1与肿瘤 [J]. 中华病理学杂志， 2002； 31(2)∶168.
27.	Kimura S, Kitadai Y, Tanaka S, et al. Expression of hypoxia-inducible factor (HIF)-1alpha is associated with vascular endothelial growth factor expression and tumour angiogenesis in human oesophageal squamous cell carcinoma [J].Eur J Cancer, 2004; 40(12)∶1904.
28.	魏海燕，陈立波，王春友. 低氧诱导因子-1a mRNA在胰腺癌组织中的表达与胰腺瘤生物学特征的关系 [J]. 癌症, 2005; 24(2)∶184.
29.	Fang J, Yan L, Shing Y, et al. HIF-1alpha-mediated up-regulation of vascular endothelial growth factor, independent of basic fibroblast growth factor, is important in the switch to the angiogenic phenotype during early tumorigenesis [J]. Cancer Res, 2001; 61(15)∶5731.
30.	李兴睿, 廖晓峰, 易继林. 缺氧对肝癌细胞系HepG2表达VEGF的影响 [J]. 中国普外基础与临床杂志, 2005; 12(5)∶477.
31.	丁磊, 陈孝平, 王海平. 肝癌和癌旁组织中HIF-1α基因蛋白的表达及其临床意义 [J]. 肝胆外科杂志， 2004; 12（1）∶32.
32.	王海平, 陈孝平, 丁磊. 缺氧诱导因子-1α与血管内皮生长因子在肝硬化、肝癌组织中的相关性研究 [J]. 中华实验外科杂志， 2004； 21（3）∶303.
33.	von Marschall Z, Cramer T, Hocker M, et al. Dual mechanism of vascular endothelial growth factor upregulation by hypoxia in human hepatocellular carcinoma [J]. Gut, 2001; 48(1)∶87.
34.	Liu LX, Lu H, Luo Y, et al. Stabilization of vascular endothelial growth factor mRNA by hypoxia-inducible factor 1 [J]. Biochem Biophys Res Commun, 2002; 291(4)∶908.

1. 　褚忠华, 闵军, 凌云彪, 等. 多种黏附分子基因在原发性肝癌的表达及其临床意义 [J]. 中国病理生理杂志， 2004； 20(9)∶1672.
2. 　王艳红，刘银坤，李文昌, 等. 抗黏附多肽对人肝癌高转移细胞系MHCC97侵袭转移的抑制作用 [J]. 中华实验外科杂志， 2004； 21（10）∶1168.
3. 　王辉, 韩亮, 李庆友. E-钙粘素和γ-连环素与原发性肝癌侵袭转移的关系 [J]. 腹部外科， 2004； 17（6）∶370.
4. 　Inayoshi J, Ichida T, Sugitani S, et al. Gross appearance of hepatocellular carcinoma reflects E-cadherin expression and risk of early recurrence after surgical treatment [J]. J Gastroenterol Hepatol, 2003; 18(6)∶673.
5. 　陈晚平, 易继林, 李兴睿, 等. 肝细胞性肝癌中E-cadherin和nm23-h1的表达与转移的关系 [J]. 临床外科杂志， 2004； 12（11）∶673.
6. 　路艳艳, 周柔丽. 整合素α6β1增强人肝癌细胞侵袭性机制的探讨 [J]. 中华肿瘤杂志， 2000； 22(4)∶287.
7. 　Tsuchiya Y, Sawada S, Tsukada K, et al. A new pseudo-peptide of Arg-Gly-Asp (RGD) inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma [J]. Int J Oncol, 2002; 20(2)∶319.
8. 　Zhou GF, Ye F, Cao LH, et al. Over expression of integrin alpha 5 beta 1 in human hepatocellular carcinoma cell line suppresses cell proliferation in vitro and tumorigenicity in nude mice [J]. Mol Cell Biochem, 2000; 207(1-2)∶49.
9. 　魏民, 曾宪录. 选择素与肿瘤转移 [J]. 生物化学与生物物理进展, 2003; 30(2)∶185.
10. 　唐南洪，陈燕凌，李秀金，等. sICAM-1、 sE-selectin水平在肝癌诊疗中的价值 [J]. 中国免疫学杂志， 2001； 17（12）∶671.
11. 　Zhang BH, Chen H, Yao XP, et al. E-selectin and its ligand-sLeX in the metastasis of hepatocellular carcinoma [J]. Hepatobiliary Pancreat Dis Int, 2002; 1(1)∶80.
12. 　刘剑勇, 张力图, 张春艳, 等. 血浆可溶性P-选择素在原发性肝癌患者中的临床意义 [J]. 临床肝胆病杂志, 2003; 19（1）∶54.
13. 　Borsig L, Wong R, Hynes RO, et al.Synergistic effects of L-and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis [J]. Proc Natl Acad Sci USA, 2002; 99(4)∶2193.
14. 　孟召伟, 方佩华. 细胞间黏附分子-1临床应用的研究进展 [J]. 天津医药， 2004； 32（11）∶714.
15. 　Xu J, Mei MH, Zeng SE, et al. Expressions of ICAM-1 and its mRNA in sera and tissues of patients with hepatocellular carcinoma [J]. World J Gastroenterol, 2001; 7(1)∶120.
16. 　彭利, 　王顺祥, 　张风瑞, 等. 基质金属蛋白酶-9和血管内皮生长因子与原发性肝癌侵袭转移关系研究 [J]. 中华肝胆外科杂志， 2003； 9（1）∶42.
17. 　Theret N, Musso O, Turlin B, et al. Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas [J]. Hepatology, 2001; 34(1)∶82.
18. 　McKenna GJ, Chen Y, Smith RM, et al. A role for matrix metalloproteinases and tumor host interaction in hepatocellular carcinomas [J]. Am J Surg, 2002; 183(5)∶588.
19. 　田波, 李雁, 冀学宁, 等. 全反式维甲酸对人肝癌高转移细胞株MHCC97-H表达基质金属蛋白酶的影响 [J]. 中华实验外科杂志， 2003; 20（10）∶900.
20. 　Aebersold DM, Burri P, Beer KT, et al. Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer [J]. Cancer Res, 2001; 61(7)∶2911.
21. 　Poon RT, Ng IO, Lau C, et al. Serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: a prospective study [J]. Ann Surg, 2001; 233(2)∶227.
22. 　刘智敏，严律南，汤宇，等. 血管内皮生长因子和基质金属蛋白酶-9在肝细胞癌中的表达及其意义 [J]. 中国普外基础与临床杂志， 2002; 9(6)∶421.
23. 　张明威，王欣，张静，等. 肝细胞肝癌中血管内皮生长因子与浸润树突状细胞表达的相关性研究 [J]. 临床肝胆病杂志， 2005； 21(5)∶288.
24. 　Ng IO, Poon RT, Lee JM, et al. Microvessel density, vascular endothelial growth factor and its receptors Flt-1 and Flk-1/KDR in hepatocellular carcinoma [J].Am J Clin Pathol, 2001; 116(6)∶838.
25. 　Yao DF, Wu XH, Zhu Y, et al. Quantitative analysis of vascular endothelial growth factor, microvascular density and their clinicopathologic features in human hepatocellular carcinoma [J]. Hepatobiliary Pancreat Dis Int, 2005; 4(2)∶220.
26. 　樊利芳，刁路明, 陈德基. 缺氧诱导因子-1与肿瘤 [J]. 中华病理学杂志， 2002； 31(2)∶168.
27. 　Kimura S, Kitadai Y, Tanaka S, et al. Expression of hypoxia-inducible factor (HIF)-1alpha is associated with vascular endothelial growth factor expression and tumour angiogenesis in human oesophageal squamous cell carcinoma [J].Eur J Cancer, 2004; 40(12)∶1904.
28. 　魏海燕，陈立波，王春友. 低氧诱导因子-1a mRNA在胰腺癌组织中的表达与胰腺瘤生物学特征的关系 [J]. 癌症, 2005; 24(2)∶184.
29. 　Fang J, Yan L, Shing Y, et al. HIF-1alpha-mediated up-regulation of vascular endothelial growth factor, independent of basic fibroblast growth factor, is important in the switch to the angiogenic phenotype during early tumorigenesis [J]. Cancer Res, 2001; 61(15)∶5731.
30. 　李兴睿, 廖晓峰, 易继林. 缺氧对肝癌细胞系HepG2表达VEGF的影响 [J]. 中国普外基础与临床杂志, 2005; 12(5)∶477.
31. 　丁磊, 陈孝平, 王海平. 肝癌和癌旁组织中HIF-1α基因蛋白的表达及其临床意义 [J]. 肝胆外科杂志， 2004; 12（1）∶32.
32. 　王海平, 陈孝平, 丁磊. 缺氧诱导因子-1α与血管内皮生长因子在肝硬化、肝癌组织中的相关性研究 [J]. 中华实验外科杂志， 2004； 21（3）∶303.
33. 　von Marschall Z, Cramer T, Hocker M, et al. Dual mechanism of vascular endothelial growth factor upregulation by hypoxia in human hepatocellular carcinoma [J]. Gut, 2001; 48(1)∶87.
34. 　Liu LX, Lu H, Luo Y, et al. Stabilization of vascular endothelial growth factor mRNA by hypoxia-inducible factor 1 [J]. Biochem Biophys Res Commun, 2002; 291(4)∶908.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Molecular Mechanism of Recurrence and Metastasis of Primary Hepatocellular Carcinoma

Abstract Full text Figures/Tables Video References Cited by

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