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.	褚忠華, 閔軍, 凌云彪, 等. 多種黏附分子基因在原發性肝癌的表達及其臨床意義 [J]. 中國病理生理雜志， 2004； 20(9)∶1672.
2.	王艷紅，劉銀坤，李文昌, 等. 抗黏附多肽對人肝癌高轉移細胞系MHCC97侵襲轉移的抑制作用 [J]. 中華實驗外科雜志， 2004； 21（10）∶1168.
3.	王輝, 韓亮, 李慶友. E-鈣粘素和γ-連環素與原發性肝癌侵襲轉移的關系 [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.	陳晚平, 易繼林, 李興睿, 等. 肝細胞性肝癌中E-cadherin和nm23-h1的表達與轉移的關系 [J]. 臨床外科雜志， 2004； 12（11）∶673.
6.	路艷艷, 周柔麗. 整合素α6β1增強人肝癌細胞侵襲性機制的探討 [J]. 中華腫瘤雜志， 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, 曾憲錄. 選擇素與腫瘤轉移 [J]. 生物化學與生物物理進展, 2003; 30(2)∶185.
10.	唐南洪，陳燕凌，李秀金，等. sICAM-1、 sE-selectin水平在肝癌診療中的價值 [J]. 中國免疫學雜志， 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.	劉劍勇, 張力圖, 張春艷, 等. 血漿可溶性P-選擇素在原發性肝癌患者中的臨床意義 [J]. 臨床肝膽病雜志, 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.	孟召偉, 方佩華. 細胞間黏附分子-1臨床應用的研究進展 [J]. 天津醫藥， 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, 　王順祥, 　張風瑞, 等. 基質金屬蛋白酶-9和血管內皮生長因子與原發性肝癌侵襲轉移關系研究 [J]. 中華肝膽外科雜志， 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, 冀學寧, 等. 全反式維甲酸對人肝癌高轉移細胞株MHCC97-H表達基質金屬蛋白酶的影響 [J]. 中華實驗外科雜志， 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.	劉智敏，嚴律南，湯宇，等. 血管內皮生長因子和基質金屬蛋白酶-9在肝細胞癌中的表達及其意義 [J]. 中國普外基礎與臨床雜志， 2002; 9(6)∶421.
23.	張明威，王欣，張靜，等. 肝細胞肝癌中血管內皮生長因子與浸潤樹突狀細胞表達的相關性研究 [J]. 臨床肝膽病雜志， 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, 陳德基. 缺氧誘導因子-1與腫瘤 [J]. 中華病理學雜志， 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，陳立波，王春友. 低氧誘導因子-1a mRNA在胰腺癌組織中的表達與胰腺瘤生物學特征的關系 [J]. 癌癥, 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.	李興睿, 廖曉峰, 易繼林. 缺氧對肝癌細胞系HepG2表達VEGF的影響 [J]. 中國普外基礎與臨床雜志, 2005; 12(5)∶477.
31.	丁磊, 陳孝平, 王海平. 肝癌和癌旁組織中HIF-1α基因蛋白的表達及其臨床意義 [J]. 肝膽外科雜志， 2004; 12（1）∶32.
32.	王海平, 陳孝平, 丁磊. 缺氧誘導因子-1α與血管內皮生長因子在肝硬化、肝癌組織中的相關性研究 [J]. 中華實驗外科雜志， 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. 　褚忠華, 閔軍, 凌云彪, 等. 多種黏附分子基因在原發性肝癌的表達及其臨床意義 [J]. 中國病理生理雜志， 2004； 20(9)∶1672.
2. 　王艷紅，劉銀坤，李文昌, 等. 抗黏附多肽對人肝癌高轉移細胞系MHCC97侵襲轉移的抑制作用 [J]. 中華實驗外科雜志， 2004； 21（10）∶1168.
3. 　王輝, 韓亮, 李慶友. E-鈣粘素和γ-連環素與原發性肝癌侵襲轉移的關系 [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. 　陳晚平, 易繼林, 李興睿, 等. 肝細胞性肝癌中E-cadherin和nm23-h1的表達與轉移的關系 [J]. 臨床外科雜志， 2004； 12（11）∶673.
6. 　路艷艷, 周柔麗. 整合素α6β1增強人肝癌細胞侵襲性機制的探討 [J]. 中華腫瘤雜志， 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, 曾憲錄. 選擇素與腫瘤轉移 [J]. 生物化學與生物物理進展, 2003; 30(2)∶185.
10. 　唐南洪，陳燕凌，李秀金，等. sICAM-1、 sE-selectin水平在肝癌診療中的價值 [J]. 中國免疫學雜志， 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. 　劉劍勇, 張力圖, 張春艷, 等. 血漿可溶性P-選擇素在原發性肝癌患者中的臨床意義 [J]. 臨床肝膽病雜志, 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. 　孟召偉, 方佩華. 細胞間黏附分子-1臨床應用的研究進展 [J]. 天津醫藥， 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, 　王順祥, 　張風瑞, 等. 基質金屬蛋白酶-9和血管內皮生長因子與原發性肝癌侵襲轉移關系研究 [J]. 中華肝膽外科雜志， 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, 冀學寧, 等. 全反式維甲酸對人肝癌高轉移細胞株MHCC97-H表達基質金屬蛋白酶的影響 [J]. 中華實驗外科雜志， 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. 　劉智敏，嚴律南，湯宇，等. 血管內皮生長因子和基質金屬蛋白酶-9在肝細胞癌中的表達及其意義 [J]. 中國普外基礎與臨床雜志， 2002; 9(6)∶421.
23. 　張明威，王欣，張靜，等. 肝細胞肝癌中血管內皮生長因子與浸潤樹突狀細胞表達的相關性研究 [J]. 臨床肝膽病雜志， 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, 陳德基. 缺氧誘導因子-1與腫瘤 [J]. 中華病理學雜志， 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，陳立波，王春友. 低氧誘導因子-1a mRNA在胰腺癌組織中的表達與胰腺瘤生物學特征的關系 [J]. 癌癥, 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. 　李興睿, 廖曉峰, 易繼林. 缺氧對肝癌細胞系HepG2表達VEGF的影響 [J]. 中國普外基礎與臨床雜志, 2005; 12(5)∶477.
31. 　丁磊, 陳孝平, 王海平. 肝癌和癌旁組織中HIF-1α基因蛋白的表達及其臨床意義 [J]. 肝膽外科雜志， 2004; 12（1）∶32.
32. 　王海平, 陳孝平, 丁磊. 缺氧誘導因子-1α與血管內皮生長因子在肝硬化、肝癌組織中的相關性研究 [J]. 中華實驗外科雜志， 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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