Novel strategies for hepatocellular carcinoma based on MMPs science

Anti-Cancer Agents in Medicinal Chemistry

Volumn 12, Issue 7, 2012, Pages 753-763

  Okazaki, Isao ^a   Inagaki, Yutaka ^b  

^a INTERNATIONAL UNIVERSITY OF HEALTH AND WELFARE   (Japan)

^b TOKAI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Alcoholic liver diseases; Anti cancer agents; Bone marrow derived stem cell; Cancer invasion; Cancer metastasis; Cancer treatment; Hepatitis b virus (HBV); Hepatitis C virus (HCV); Hepatocellular carcinoma (HCC); Matrix metalloproteinase (MMP); Non alcoholic liver diseases; Tissue inhibitor of metalloproteinase (TIMP)

Indexed keywords

5 (N ETHYL N ISOPROPYL)AMILORIDE; ADIPONECTIN; ANTINEOPLASTIC AGENT; BACOSIDE A; CHRYSANTHEMUM EXTRACT; COLLAGENASE 3; GELATINASE A; GELATINASE B; HESPERIDIN; HISPOLON; INTERSTITIAL COLLAGENASE; ISOFRAXIDIN; LEPTIN; LYSOPHOSPHATIDIC ACID; MACROPHAGE ELASTASE; MATRILYSIN; MATRIX METALLOPROTEINASE; MENATETRENONE; MICRORNA 21; MITOGEN ACTIVATED PROTEIN KINASE P38; MORIN; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; POLYPHENON B; PROTEIN KINASE C; PTEROSTILBENE; RECOMBINANT BONE MORPHOGENETIC PROTEIN 2; SMALL INTERFERING RNA; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TISSUE INHIBITOR OF METALLOPROTEINASE 2; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER GROWTH; CANCER INVASION; CANCER STAGING; CANCER STEM CELL; CELL DEDIFFERENTIATION; CELL DIFFERENTIATION; CELL INFILTRATION; CHRYSANTHEMUM INDICUM; ENDOTHELIUM CELL; ENZYME LOCALIZATION; HEPATOMA CELL; HISTOPATHOLOGY; HUMAN; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER FIBROSIS; MESENCHYME CELL; METASTASIS; NONHUMAN; NORTHERN BLOTTING; PATHOGENESIS; PROTEIN EXPRESSION; REGULATORY MECHANISM; SCIENCE; SIGNAL TRANSDUCTION; STROMA CELL; TISSUE MICROARRAY; TUMOR GROWTH;

EID: 84866369296     PISSN: 18715206     EISSN: 18755992     Source Type: Journal    
DOI: 10.2174/187152012802650165     Document Type: Article

References (95)

1. Parkin, D. M.; Bray, F.; Ferlay, J.; Pisani, P. Global cancer statistics, 2002. CA. Cancer J. Clin., 2005, 55(2), 74-108.
2. Venook, A. P.; Papandreou, C.; Furuse, J.; de Guevara, L. L. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist, 2010, 15 (Suppl. 4), 5-13.
3. Okuda, K.; Takayasu, K. In: Hepatobiliary Diseases. Pathophysiology and Imaging; Okuda, K.; Mitchell, D. G.; Itai, Y.; Ariyama, J., Ed; Blackwell Science, 2001, Oxford, pp. 343-389.
4. Marrero, J. A.; Kudo, M.; Bronowicki, J. The challenge of prognosis and staging for hepatocellular carcinoma. Oncologist, 2010, 15 (Suppl. 4), 23-33.
5. Yang, J. D.; Roberts, L. R. Hepatocellular carcinoma: A global view. Nat. Rev. Gastroenterol. Hepatol., 2010, 7(8), 448-458.
6. Okazaki, I.; Maruyama, K. Collagenase activity in experimental hepatic fibrosis. Nature (London), 1974, 252(5478), 49-50.
7. Okazaki, I.; Brinckerhoff, C. E.; Sinclair, J. R.; Sinclair, P. R.; Bonkovsky, H. L.; Harris, E. D., Jr. Iron increases collagenase production by rabbit synovial fibroblasts. J. Lab. Clin. Med., 1981, 97(3), 396-402.
8. Maruyama, K.; Feinman, L.; Okazaki, I.; Lieber, C. S. Direct measurement of neutral collagenase activity in homogenates from baboon and human liver. Biochim. Biophys. Acta, 1981, 658(1), 124-131.
9. Maruyama, K.; Okazaki, I.; Kobayashi, T.; Suzuki, H.; Kashiwazaki, K.; Tsuchiya, M. Collagenase production by rabbit liver cells in monolayer culture. J. Lab. Clin. Med., 1983, 102(4), 543-550.
10. Arai, M.; Niioka, M.; Maruyama, K.; Wada, N.; Fujimoto, N.; Nomiyama, T.; Tanaka, S.; Okazaki, I. Changes in serum levels of metalloproteinases and their inhibitors by treatment of chronic hepatitis C with interferon. Dig. Dis. Sci., 1996, 41(5), 995-1000.
11. Watanabe, T.; Niioka, M.; Hozawa, S.; Kameyama, K.; Hayashi, T.; Arai, M.; Ishikawa, A. Gene expression of interstitial collagenase in both progressive and recovery phase of rat liver fibrosis induced by carbon tetrachloride. J. Hepatol., 2000, 33(2),224-235.
12. Watanabe, T.; Niioka, M.; Ishikawa, A.; Hozawa, S.; Arai, M.; Maruyama, K.; Okada, A.; Okazaki, I. Dynamic change of cells expressing MMP-2 mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat. J. Hepatol., 2001, 35(4), 465-473.
13. Watanabe, T.; Niioka, M.; Hozawa, S.; Sugioka, Y.; Arai, M.; Maruyama, K.; Okano, H.; Okazaki, I. In: Extracellular Matrix and the Liver-Approach to Gene Therapy; Okazaki, I.; Ninomiya, Y.; Friedman, S. L.; Tanikawa, K., Ed.; Academic Press, New York, 2003, pp. 362-388.
14. Inagaki, Y.; Nemoto, T.; Nakao, A. In: Extracellular Matrix and the Liver-Approach to Gene Therapy; Okazaki, I.; Ninomiya, Y.; Friedman, S. L.; Tanikawa, K., Ed.; Academic Press, New York, 2003, pp. 233-248.
15. Inagaki, Y.; Nemoto, T.; Kushida, M.; Sheng, Y.; Higashi, K.; Ikeda, K.; Kawada, N.; Shirasaki, F.; Takehara, K.; Sugiyama, K.; Fujii, M.; Yamauchi, H.; Nakao, A.; de Chrobrughe, B.; Watanabe, T.; Okazaki, I. Interferon alpha down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis. Hepatology, 2003, 38(4), 890-899.
16. Inagaki, Y.; Kushida, M.; Higashi, K.; Itoh, J.; Kawada, N.; Namikawa, K.; Kiyama, H.; Bou-Gharious, G.; Higashiyama, R.; Watanabe, T.; Okazaki, I.; Ikeda, K. Cell type-specific intervention of transforming growth factor beta/Smad signaling suppresses collagen gene expression and hepatic fibrosis in mice. Gastroenterology, 2005, 129(1), 259-268.
17. Higashiyama, R.; Inagaki, Y.; Hong, Y.Y.; Kushida, M.; Nakao, S.; Niioka, M.; Watanabe, T.; Matsuzaki, Y.; Okano, H.; Shiota, G.; Okazaki, I. Bone marrow-derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice. Hepatology, 2007, 45(1), 213-222.
18. Inagaki, Y.; Okazaki, I. Emerging insights into Transforming growth factor beta Smad signal in hepatic fibrogenesis. Gut, 2007, 56(2), 284-292.
19. Inagaki, Y.; Kushida, M.; Shiota, G.; Kuwabara, I.; Itoh, J.; Moro, T.; Hong, Y.Y.; Nakao, S.; Higashiyama, R.; Okazaki, I.; Mikami, T.; Kimura, T.; Higashi, K. Hepatocyte growth factor suppresses profibrogenic signal transduction via nuclear export of Smad3 with galectin-7. Gastroenterology, 2008, 134(4), 1180-1190.
20. Moro, T.; Shimoyama, Y.; Kushida, M.; Hong, Y. Y.; Nakao, S.; Higashiyama, R.; Sugioka, Y.; Inoue, H.; Okazaki, I.; Inagaki, Y. Glycyrrhizin and its metabolite inhibit Smad3-mediated type 1 collagen gene transcription and suppress experimental murine liver fibrosis. Life Sci., 2008, 83(15-16), 531-539.
21. Higashiyama, R.; Moro, T.; Nakao, S.; Mikami, K.; Fukumitsu, H.; Ikeda, K.; Adachi, E.; Bou-GGharios, G.; Okazaki, I.; Inagaki, Y. Negligible contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice. Gastroenterology, 2009, 137(4), 1459-1466.
22. Okazaki, I.; Wada, N.; Nakano, M.; Sato, A.; Takasaki, K.; Doi, M.; Kameyama, K.; Otani, Y.; Kubochi, K.; Niioka, M.; Watanabe, T.; Maruyama K. Difference in gene expression for matrix metalloproteinase-1 between early and advanced hepatocellular carcinomas. Hepatology, 1997, 25(3), 580-584.
23. Sugioka, Y.; Watanabe, T.; Inagaki, Y.; Kushida, M.; Niioka, M.; Endo, H.; Higashiyama, R.; Okazaki, I. C-Jun NH2-terminal kinase pathway is involved in constitutive matrix metalloproteinase-1 expression in a hepatocellular carcinoma-derived cell line. Int. J. Cancer, 2004, 109(6), 867-874.
24. Endo, H.; Watanabe, T.; Sugioka, Y.; Niioka, M.; Inagaki, Y.; Okazaki, I. Activation of two distinct MAPK pathways governs constitutive expression of matrix metalloproteinase-1 in human pancreatic cancer cell lines. Int. J. Oncol., 2009, 35(6), 1237-1245.
25. Kenmochi, K.; Sugihara, S.; Kojiro, M. Relationship of histologic grade of hepatocellular carcinoma (HCC) to tumor size, and demonstration of tumor cells of multiple different grades in single small HCC. Liver, 1987, 7(1), 18-26.
26. Tomizawa, M.; Kondo, F.; Kondo, Y. Growth patterns and interstitial invasion of small hepatocellular carcinoma. Pathol. Int., 1995, 45(5), 352-358.
27. Takayama, T.; Makuuchi, M.; Hirohashi, S.; Sakamoto, M.; Okazaki, N.; Takayasu, K.; Kosuge, T.; Motoo, Y.; Yamazaki, S.; Hasegawa, H. Malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma. Lancet, 1990, 336(8724), 1150-1153.
28. Sakamoto, M.; Hirohashi, S.; Shimosato, Y. Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma. Hum. Pathol.,1991, 22(2), 172-178.
29. Sugihara, S.; Nakashima, O.; Kojiro, M.; Majima, Y.; Tanaka, M.; Tanikawa, K. The morphologic transition in hepatocellular carcinoma. A comparison of the individual histologic features disclosed by ultrasound-guided fine-needle biopsy with those of autopsy. Cancer, 1992, 70(86), 1488-1492.
30. Liotta, L. A. Tumor invasion and metastasis -role of the extracellular matrix: Rhoads Memorial Award Lecture. Cancer Res., 1986, 46(1), 1-7.
31. Sato, H.; Kida, Y.; Mai, M.; Endo, Y.; Sasaki, T.; Tanaka, J.; Seiki, M. Expression of genes encoding type IV collagen-degrading metalloproteinases and tissue inhibitors of metalloproteinases in various human tumor cells. Oncogene, 1992, 7(1), 77-83.
32. Grigioni, W. F.; Garbisa, S.; D'Errico, A.; Baccarini, P.; Stetler-Stevenson, W. G.; Liotta, L. A.; Mancini, A. M. Evaluation of hepatocellular carcinoma aggressiveness by a panel of extracellular matrix antigens. Am. J. Pathol., 1991, 138(3), 647-654.
33. Terada, T.; Okada, Y.; Nakanuma, Y. Expression of immunoreactive matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human normal livers and primary liver tumors. Hepatology, 1996, 23(6), 1341-1344.
34. Arii, S.; Mise, M.; Harada, T.; Furutani, M.; Ishigami, S.; Niwano, M.; Mizumoto, M.; Fukumoto, M.; Imamura, M. Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential. Hepatology, 1996, 24(2), 316-322.
35. Nakatsukasa, H.; Ashida, K.; Higashi, T.; Ohguchi, S.; Tsuboi, S.; Hino, N.; Nouso, K.; Urabe, Y.; Kinugasa, N.; Yoshida, K.; Uematsu, S.; Ishizaki, M.; Kobayashi, Y.; Tsuji, T. Cellular distribution of transcripts for tissue inhibitor of metalloproteinases 1 and 2 in human hepatocellular carcinomas. Hepatology, 1996, 24(1), 82-88.
36. Yamamoto, H.; Itoh, F.; Adachi, Y.; Sakamoto, H.; Adachi, M.; Hinoda, Y.; Imai, K. Relation of enhanced secretion of active matrix metalloproteinases with tumor spread in human hepatocellular carcinoma. Gastroenterology, 1997, 112(4), 1290-1296.
37. Musso, O.; Theret, N.; Campion, J. P.; Turlin, B.; Milani, S.; Grappone, C.; Clement, B. In situ detection of matrix metalloproteinase-2 (MMP2) and the metalloproteinase inhibitor TIMP2 transcripts in human primary hepatocellular carcinoma and in liver metastasis. J. Hepatol., 1997, 26(3), 593-605.
38. Harada, T.; Arii, S.; Imamura, T.; Higashitsuji, H.; Furutani, M.; Niwano, M.; Ishigami, S.; Fukumoto, M.; Seiki, M.; Sato, H.; Imamura, M. Membrane-type matrix metalloproteinase-1 (MT1-MMP) gene is overexpressed in highly invasive hepatocellular carcinoma. J. Hepatol., 1998, 28(2), 231-239.
39. Theret, N.; Musso, O.; L'Helgoualc'h, A.; Campion, J-P.; Clement, B. Differential expression and origin of membrane-type 1 and 2 matrix metalloproteinases (MT-MMPs) in association with MMP2 activation in injured human livers. Am. J. Pathol., 1998, 153(3), 945-954.
40. Gorrin Rivas, M. J. G.; Arii, S.; Furutani, M.; Harada, T.; Mizumoto, M.; Nishiyama, H.; Fujita, J.; Imamura, M. Expression of human macrophage metalloelastase gene in hepatocellular carcinoma: correlation with angiostatin generation and its clinical significance. Hepatology, 1998, 28(4), 986-993.
41. Yamamoto, H.; Itoh, F.; Adachi, Y.; Fukushima, H.; Itoh, H.; Sasaki, S.; Hinoda, Y.; Imai, K. Messenger RNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human hepatocellular carcinoma. Jpn. J. Clin. Oncol., 1999, 29(2), 58-62.
42. Ogata, R.; Torimura, T.; Kin, M.; Ueno, T.; Tateishi, Y.; Kuromatsu, R.; Shimauchi, Y.; Sakamoto, M.; Tamaki, S.; Sata, M.; Tanikawa, K. Increased expression of membrane type 1 matrix metalloproteinases and matrix metalloproteinase-2 with tumor differentiation in hepatocellular carcinomas. Hum. Pathol., 1999, 30(4), 443-450.
43. Ashida, K.; Nakatsukasa, H.; Higashi, T.; Ohguchi, S.; Hino, N.; Nouso, K.; Urabe, Y.; Yoshida, K.; Kinugasa, N.; Tsuji, T. Cellular distribution of 92-kd type IV collagenase B in human hepatocellular carcinoma. Am. J. Pathol., 1996, 149(6), 1803-1811.
44. Sakamoto, Y.; Mafune, K.; Mori, M.; Shiraishi, T.; Imamura, H.; Mori, M.; Takayama, T.; Makuuchi, M. Overexpression of MMP-9 correlates with growth of small hepatocellular carcinoma. Int. J. Oncol., 2000, 17(2), 237-243.
45. Maatta, M.; Soini, Y.; Liakka, A.; Autio-Harmainen, H. Differential expression of matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP in hepatocellular and pancreatic adenocarcinoma: Implications for tumor progression and clinical prognosis. Clin. Cancer Res., 2000, 6(7), 2726-2734.
46. McKenna, G. J.; Chen, Y.; Smith, R. M.; Meneghetti, A.; Ong, C.; McMaster, R.; Scudamore, C. H.; Chung, S. W. A role for matrix metalloproteinases and tumor host interaction in hepatocellular carcinomas. Am. J. Surg., 2002, 183(5), 588-594.
47. Giannelli, G.; Bergamini, C.; Marinosci, F.; Fransvea, E.; Quaranta, M.; Lupo, L.; Schiraldi, O.; Antonaci, S. Clinical role of MMP-2/TIMP-2 imbalance in hepatocellular carcinoma. Int. J. Cancer, 2002, 97(4), 425-431.
48. Ishii, Y.; Nakasato, Y.; Kobayashi, S.; Yamazaki, Y.; Aoki, T. A study on angiogenesis-related marix metalloproteinase networks in primary hepatocellular carcinoma. J. Exp. Clin. Cancer Res., 2003, 22(3), 461-470.
49. Gao, Z. H.; Tretiakova, M. S.; Liu, W. H.; Gong, C.; Farris, P. D.; Hart, J. Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma. Mod. Pathol., 2006, 19(4), 533-540.
50. Altadill, A.; Rodriguez, M.; Gonzalez, L. O.; Junquera, S.; Corte, M. D.; Gonzalez-Dieguez, M. L.; Linares, A.; Barbon, E.; Fresno-Forcelledo, M.; Rodrigo, L.; Vizoso, F. J. Liver expression of matrix metalloproteinases and their inhibitors in hepatocellular carcinoma. Dig. Liver Dis., 2009, 41(10), 740-748.
51. Tretiakova, M. S.; Hart, J.; Shabani-Rad, M. T.; Zhang, J.; Gao, Z. Distinction of Hepatocellular adenoma from hepatocellular carcinoma with and without cirrhosis using E-cadherin and matrix metalloproteinase. Mod. Pathol., 2009, 22(8), 1113-1120.
52. Okazaki, I.; Watanabe, T.; Niioka, M.; Sugioka, Y.; Inagaki, Y. In: Fibrogenesis: Cellular and Molecular Basis; Razzaque, M. S., Ed.; Landes Bioscience/Kluwer Acad. Plenum Press, New York, 2005, pp. 143-159.
53. Sato, H.; Takino, T.; Okada, Y.; Cao, J.; Shinagawa, A.; Yamamoto, E.; Seiki, M. A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature, 1994, 370(6484), 61-65.
54. Strongin, A. Y.; Collier, I.; Bannikov, G.; Marmer B. L.; Grant, G. A.; Goldberg, G. I. Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloproteinase. J. Biol. Chem., 1995, 270(10), 5331-5338.
55. Benbow, U.; Brinckerhoff, C. In: Extracellular Matrix and the Liver-Approach to Gene Therapy; Okazaki, I.; Ninomiya, Y.; Friedman, S. L.; Tanikawa, K., Ed.; Academic Press, New York, 2003, pp. 277-297.
56. Ide, Y.; Zhang, H.; Hamajima, H.; Kawaguchi, Y.; Eguchi, Y.; Mizuta, T.; Yamamoto, K.; Fujimoto, K.; Ozaki, I. Inhibition of matrix metalloproteinase expression by menatetrenone, a vitamin K2 analogue. Oncol. Reports, 2009, 22(3), 599-604.
57. Stefanou, N.; Papanikolaou, V.; Fukukawa, Y.; Nakamura, Y.; Tsezou, A. Leptin as a critical regulator of hepatocellular carcinoma development through modulation of human telomerase reverse transcriptase. BMC Cancer, 2010, 10(Aug 19), 442-452.
58. Jia, L.; Xu, H.; Zhao, Y.; Jiang, L.; Yu, J.; Zhang, J. Expression of CD147 mediates tumor cells invasion and multidrug resistance in hepatocellular carcinoma. Cancer Invest., 2008, 26(10), 977-983.
59. Akutsu, N.; Yamamoto, H.; Sasaki, S.; Taniguchi, H.; Arimura, Y.; Imai, K.; Shinomura, Y. Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma. World J. Gastroenterology, 2010, 16(28), 3521-3528.
60. Chen, Y.; Boyartchuk, V.; Lewis, B. Differential roles of insulinlike growth factor receptor- and insulin receptor-mediated signaling in the phenotypes of hepatocellular carcinoma cells. Neoplasia, 2009, 11(9), 835-845.
61. Shengbing, Z.; Feng, L. J.; Bin, W.; Lingyun, G.; Aimin, H. Expression of KISS-1 gene and its role in invasion and metastasis of human hepatocellular carcinoma. Anat. Rec. (Hoboken), 2009, 292(8), 1128-1134.
62. Tian, T.; Nan, K.; Guo, H.; Wang, W.; Ruan, Z.; Wang, S.; Liang, X.; Lu, C. PTEN inhibits the migration and invasion of HepG2 cells by coordinately decreasing MMP expression via the PI3K/Akt pathway. Oncol. Rep., 2010, 23(6), 1593-1600.
63. Park, S. Y.; Jeong, K. J.; Panupinthu, N.; Yu, S.; Lee, J.; Han, J. V. V.; Kim, J. M.; Lee, J. S.; Kang, J.; Park, C. G.; Mills, G. B.; Lee, H. Y. Lysophospatidic-acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP-9 expression. Oncogene, 2011, 30(11), 1351-1359.
64. Yang, X.; Wang, D.; Dong, W.; Song, Z.; Dou, K. Inhibition of Na(+)/H(+) exchanger 1 by 5-(N-ethyl-N-isopropyl) amiloride reduces hypoxia-induced hepatocellular carcinoma invasion and motility. Cancer Letter, 2010, 295(2), 198-204.
65. Kessenbrock, K.; Plaks, V.; Werb, Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell, 2010, 141(1), 52-67.
66. Murugan, R. S.; Vinothini, G.; Hara, Y.; Nagini, S. Black tea polyphenols target matrix metalloproteinases, RECK, proangiogenic molecules and histone deacetylase in a rat hepatocarcinogenesis model. Anticancer Res., 2009, 29(6), 2301-2305.
67. Fu, J.; Chen, Y.; Cao, J.; Luo, T.; Qian, Y.; Yang, W.; Ren, Y.; Su, B.; Cao, G.; Yang, Y.; Yan, Y.; Shen, F.; Wu, M.; Feng, G.; Wang, H. P28 GANK overexpression accelerates hepatocellular carcinoma invasiveness and metastasis via phosphoinositol 3-kinae /AKT/hypoxia-inducible factor-1α pathways. Hepatology, 2011, 53(1), 181-192.
68. Hayashi, Y.; Osanai, M.; Lee, G. H. Fascin-1 expression correlates with repression of E-cadherin expression in hepatocellular carcinoma cells and augments their invasiveness in combination with matrix metalloproteinases. Cancer Sci., 2011, 102(6), 1226-1235.
69. Man, K.; Ng, K. T. P.; Xu, A.; Cheng, Q.; Lo, C. M.; Xiao, J. W.; Sun, B. S.; Lim, Z. X. H.; Cheung, J. S.; Wu, E. X.; Sun, C. K W.; Poon, R. T. P.; Fan, S. T. Suppression of tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling. Clin. Cancer Res., 2010, 16(3): 967-977.
70. Martin, D. C.; Sanchez-Swatman, O. H.; Ho, A. T.; Inderdeo, D. S.; Tsao, M., Khokha, R. Transgenic TIMP-1 inhibits simian virus 40 T antigen-induced hepatocarcinogenesis by impairment of hepatocellular proliferation and tumor angiogenesis. Lab. Invest., 1999, 79(2), 225-234.
71. Wang, B.; Hsu, S.; Majumder, S.; Kutay, H.; Huang, W.; Jacob, S. T.; Ghoshal, K. TGFbeta-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene, 2010, 29(12), 1787-1797.
72. Wang, Z.; Huang, C.; Li, Z.; Yang, J.; Li, B.; Liang, R.; Dai, Z.; Liu, Z. Chrysanthemum indicum ethanolic extract inhibits invasion of hepatocellular carcinoma via regulation of MMP/TIMP balance as therapeutic target. Oncology Reports, 2010, 23(2), 413-421.
73. Pan M.; Chiou, Y.; Chen, W.; Wang, J.; Badmaev, V.; Ho, C. Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. Carcinogenesis, 2009, 30(7), 1234-1242.
74. Sivaramakrishnan, V.; Niranjali Devaraj, S. Morin regulates the expression of NF-kappaB-p65, COX-2 and matrix metalloproteinases in diethylnitrosamine induced rat hepatocellular carcinoma. Chem. Biol. Interact., 2009, 180(3), 353-359.
75. Lee, K.; Yeh, M.; Kao S.; Hung, C.; Liu, C.; Huang, Y.; Yeh, C. The inhibitory effect of hesperidin on tumor cell invasiveness occurs via suppression of activator protein 1 and nuclear factorkappaB in human hepatocellular carcinoma cells. Toxicol. Lett., 2010, 194(1-2), 42-49.
76. Huang, G.; Yang, C.; Chang, Y.; Amagaya, S.; Wang, H.; Hou, W.; Huang, S.; Hu, M. Hispolon suppresses SK-Hep1 human hepatoma cell metastasis by inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt and ERK signaling pathways. J. Agric. Food Chem., 2010, 58(17), 9468-9475.
77. Janani, P.; Silvakumari, K.; Geetha, A.; Yuvaraj, S.; Parthasarathy, C. Bacoside A downregulates matrix metalloproteinases 2 and 9 in DEN-induced hepatocellular carcinoma. Cell Biochem. Funct, 2010, 28(2), 164-169.
78. Wu, J. B.; Huang, L. Z.; Liu, A. W.; Zhang, J. X. Effects of siRNA-targeting BMP-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells and its mechanism. Cancer Gene Ther., 2011, 18(1), 20-25.
79. Yamazaki, T.; Tokiwa, T. Isofraxidin, a coumarin component from Acanthopanax senticosus, inhibits matrix metalloproteinase-7 expression and cell invasion of human hepatoma cells. Biol. Pharm. Bull., 2010, 33(10), 1716-1722.
80. Meng, F.; Henson, R.; Wehbe-Janek, H.; Ghoshal, K.; Jacob, S. T.; Patel, T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology, 2007, 133(2), 647-658.
81. Chen, R.; Xia, Y.; Xue, T.; Zhang, H.; Ye, S. Down-regulation of osteopontin inhibits metastasis of hepatocellular carcinoma cells via a mechanism involving MMP-2 and uPA. Oncol. Reports, 2011, 25(3), 803-808.
82. Lee, E.; Kim, H.; Lee, K.; Lee, H.; Lee, J.; Kim, D.; Hong, S.; Yoon, Y.; Kim, J. Inhibition of the proliferation and invasion of hepatocellular carcinoma cells by lipocalin 2 through blockade of JNK and PI3K/Akt signaling. Int, J. Oncol., 2011, 38(2), 325-333.
83. Tang, N. H.; Chen, Y. L.; Wang, X. Q.; Li, X. J.; Wu, Y.; Zou, Q. L.; Chen, Y. Z. N-terminal and C-terminal heparin-binding domain polypeptides derived from fibronectin reduce adhesion and invasion of liver cancer cells. BMC Cancer, 2010, 10(Oct. 3), 552, 1-13.
84. Muhlebach, M. D.; Schaser, T.; Zimmermann, M.; Armeanu, S.; Hanschmann, K. O.; Cattaneo, R.; Bitzer, M.; Lauer, U. M.; Cichutek, K.; Buchholtz, C. J. Liver cancer protease activity profiles support therapeutic options with matrix metalloproteinaseactivable oncolytic measles virus. Cancer Res., 2010, 70(19), 7620-7629.
85. Eferl, R.; Ricci, R.; Kenner, L.; Zenz, R.; David, J. P.; Rath, M.; Wagner, E. F. Liver tumor development. C-Jun antagonizes the proapoptotic activity of p53. Cell, 2003, 112(2), 181-192.
86. Chen, X.; Lingala, S.; Khoobyari, S.; Nolta, J.; Zern, M. A.; Wu, J. Epithelial mesenchymal transition and hedgehog signaling activation are associated with chemoresistance and invasion of hepatoma subpopulations. J. Hepatol., 2011, 55(4), 838-845.
87. Ma, S.; Chan, W.; Hu, L.; Lee, T. K.; Wo, J. Y.; Ng, I. O.; Zheng, B. J.; Guan, X. Y. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology, 2007, 132(7), 2542-2556.
88. Kohga, K.; Tatsumi, T.; Takehara, T.; Tsunematsu, H.; Shimizu, S.; Yamamoto, M.; Sasakawa, A.; Miyagi, T.; Hayashi, Y. Expression of CD133 confers malignant potential by regulating metalloproteinases in human hepatocellular carcinoma. J. Hepatol., 2010, 52(6), 872-879.
89. Na, D. C.; Lee, J. E.; Yoo, J. E.; Oh, B.; Choi, G. H.; Park, Y. N. Invasion and EMT-associated genes are up-regulated in B viral hepatocellular carcinoma with high expression of CD133-human and cell culture study. Exp. Mol. Pathol., 2011, 90(1), 66-73.
90. Shrivastava, A.; Manna, S. K.; Ray, R.; Aggarval, B. B. Ectopic expression of hepatitis C virus core protein differentially regulates nclear transcription factors. J.Virology, 1998, 72(12), 9722-9728.
91. Pereira, Tde A.; Witek, R. P.; Sin, W. K.; Choi, S. S.; Bradrick, S.; Karaca, G. F.; Agboola, K. M.; Jung, Y.; Omenetti, A.; Moylan, C. A.; Yang, L.; Femandez-zapico, M. E.; Jhaveri, R.; Shah, V. H.; Pereira, F. E.; Diehl, A. M. Viral factors induce Hedgehog pathway activation in humans with viral hepatitis, cirrhosis, and hepatocellular carcinoma. Lab Invest., 2010, 90(12), 1690-1703.
92. Machida, K. TLRs, Alcohol, HCV, and Tumorigenesis. Gastroenterol. Res. Prac., 2010, ID 518674, Epub 2011 Feb 9, 8 pages.
93. Quante, M.; Tu, S. P.; Tomita, H.; Gonda, T.; Wang, S. S. W.; Takashi, S.; Baik, G. H.; Shibata, W.; DiPrete, B.; Betz, K. S.; Friedman, R.; Varro, A.; Tycko, B.; Wang, T. C. Bone marrowderived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell, 2011, 19(2), 257-272.
94. Das, M.; Garlick, D. S.; Greiner, D. L.; Davis, R. J. The role of JNK in the development of hepatocellular carcinoma. Genes Develop., 2011, 25(6), 634-645.
95. Okazaki, I.; Watanabe, T.; Hozawa, S.; Niioka, M.; Arai, M.; Maruyama, K. Reversibility of hepatic fibrosis: from the first report of collagenase in the liver to the possibility of gene therapy for recovery. Keio J. Med., 2001, 50(2), 58-65.