Metformin prevents hepatocellular carcinoma development by suppressing hepatic progenitor cell activation in a rat model of cirrhosis

Cancer

Volumn 122, Issue 8, 2016, Pages 1216-1227

  Deperalta, Danielle K ^a   Wei, Lan ^a   Ghoshal, Sarani ^a   Schmidt, Benjamin ^a   Lauwers, Gregory Y ^a   Lanuti, Michael ^a   Chung, Raymond T ^b   Tanabe, Kenneth K ^a   Fuchs, Bryan C ^a  

^a MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

hepatocellular carcinoma (HCC); liver; oval cells; prevention; receptor for advanced glycation end products (RAGE)

Indexed keywords

ADENYLATE KINASE; ADVANCED GLYCATION END PRODUCT RECEPTOR; ALPHA SMOOTH MUSCLE ACTIN; CD68 ANTIGEN; COLLAGEN TYPE 1; COLLAGEN TYPE 1 ALPHA 1; CXCL16 CHEMOKINE; HERMES ANTIGEN; METFORMIN; MONOCYTE CHEMOTACTIC PROTEIN 1; OSTEOPONTIN; SOMATOMEDIN C; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TRANSFORMING GROWTH FACTOR BETA1; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN EXPRESSION; ARTICLE; CANCER INCIDENCE; CELL ACTIVATION; CELL SELF-RENEWAL; CHEMOPROPHYLAXIS; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; GENE EXPRESSION; HEPATIC PROGENITOR CELL; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; ANIMAL; CARCINOMA, HEPATOCELLULAR; CELL TRANSFORMATION; COMPARATIVE STUDY; CYTOLOGY; DISEASE MODEL; DRUG EFFECTS; ENZYME LINKED IMMUNOSORBENT ASSAY; IMMUNOHISTOCHEMISTRY; LIVER NEOPLASMS; NEEDLE BIOPSY; PATHOLOGY; POLYMERASE CHAIN REACTION; PROCEDURES; RANDOMIZATION; REFERENCE VALUE; STEM CELL; TREATMENT OUTCOME; WESTERN BLOTTING; WISTAR RAT;

ANIMALS; BIOPSY, NEEDLE; BLOTTING, WESTERN; CARCINOMA, HEPATOCELLULAR; CELL TRANSFORMATION, NEOPLASTIC; DISEASE MODELS, ANIMAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; IMMUNOHISTOCHEMISTRY; LIVER CIRRHOSIS; LIVER NEOPLASMS; MALE; METFORMIN; POLYMERASE CHAIN REACTION; RANDOM ALLOCATION; RATS; RATS, WISTAR; REFERENCE VALUES; STEM CELLS; TREATMENT OUTCOME;

EID: 84959432248     PISSN: 0008543X     EISSN: 10970142     Source Type: Journal    
DOI: 10.1002/cncr.29912     Document Type: Article

References (48)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D,. Global cancer statistics. CA Cancer J Clin. 2011; 61: 69-90.
2. El-Serag HB,. Hepatocellular carcinoma. N Engl J Med. 2011; 365: 1118-1127.
3. Polesel J, Zucchetto A, Montella M, et al., The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Ann Oncol. 2009; 20: 353-357.
4. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD,. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005; 330: 1304-1305.
5. Decensi A, Puntoni M, Goodwin P, et al., Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res. 2010; 3: 1451-1461.
6. Currie CJ, Poole CD, Jenkins-Jones S, Gale EA, Johnson JA, Morgan CL,. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care. 2012; 35: 299-304.
7. Jiralerspong S, Palla SL, Giordano SH, et al., Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 2009; 27: 3297-3302.
8. Owen MR, Doran E, Halestrap AP,. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000; 348: 607-614.
9. El-Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X,. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem. 2000; 275: 223-228.
10. El-Serag HB, Tran T, Everhart JE,. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology. 2004; 126: 460-468.
11. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB,. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut. 2005; 54: 533-539.
12. Donadon V, Balbi M, Ghersetti M, et al., Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease. World J Gastroenterol. 2009; 15: 2506-2511.
13. Donadon V, Balbi M, Mas MD, Casarin P, Zanette G,. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease. Liver Int. 2010; 30: 750-758.
14. Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH, Huang YC,. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals [serial online]. BMC Cancer. 2011; 11: 20.
15. Zhang ZJ, Zheng ZJ, Shi R, Su Q, Jiang Q, Kip KE,. Metformin for liver cancer prevention in patients with type 2 diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2012; 97: 2347-2353.
16. Chen HP, Shieh JJ, Chang CC, et al., Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. Gut. 2013; 62: 606-615.
17. Singh S, Singh PP, Singh AG, Murad MH, Sanchez W,. Anti-diabetic medications and the risk of hepatocellular cancer: a systematic review and meta-analysis. Am J Gastroenterol. 2013; 108: 881-891.
18. Quinn BJ, Kitagawa H, Memmott RM, Gills JJ, Dennis PA,. Repositioning metformin for cancer prevention and treatment. Trends Endocrinol Metab. 2013; 24: 469-480.
19. Pollak MN,. Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov. 2012; 2: 778-790.
20. Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K,. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009; 69: 7507-7511.
21. Bednar F, Simeone DM,. Metformin and cancer stem cells: old drug, new targets. Cancer Prev Res. 2012; 5: 351-354.
22. Cheng J, Huang T, Li Y, et al., AMP-activated protein kinase suppresses the in vitro and in vivo proliferation of hepatocellular carcinoma [serial online]. PLoS One. 2014; 9: e93256.
23. Bhalla K, Hwang BJ, Dewi RE, et al., Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis. Cancer Prev Res. 2012; 5: 544-552.
24. Fuchs BC, Hoshida Y, Fujii T, et al., Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma. Hepatology. 2014; 59: 1577-1590.
25. Ishak K, Baptista A, Bianchi L, et al., Histological grading and staging of chronic hepatitis. J Hepatol. 1995; 22: 696-699.
26. Kita Y, Takamura T, Misu H, et al., Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis [serial online]. PLoS One. 2012; 7: e43056.
27. Roskams T,. Liver stem cells and their implication in hepatocellular and cholangiocarcinoma. Oncogene. 2006; 25: 3818-3822.
28. Ziol M, Nault JC, Aout M, et al., Intermediate hepatobiliary cells predict an increased risk of hepatocarcinogenesis in patients with hepatitis C virus-related cirrhosis. Gastroenterology. 2010; 139: 335-343.
29. Yang W, Wang C, Lin Y, et al., OV6(+) tumor-initiating cells contribute to tumor progression and invasion in human hepatocellular carcinoma. J Hepatol. 2012; 57: 613-620.
30. Yamashita T, Wang XW,. Cancer stem cells in the development of liver cancer. J Clin Invest. 2013; 123: 1911-1918.
31. Pusterla T, Nemeth J, Stein I, et al., Receptor for advanced glycation end products (RAGE) is a key regulator of oval cell activation and inflammation-associated liver carcinogenesis in mice. Hepatology. 2013; 58: 363-373.
32. Xu X, Liu RF, Zhang X, et al., DLK1 as a potential target against cancer stem/progenitor cells of hepatocellular carcinoma. Mol Cancer Ther. 2012; 11: 629-638.
33. Tajima K, Nakamura A, Shirakawa J, et al., Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 mice [serial online]. Am J Physiol Endocrinol Metab. 2013; 305: E987-E998.
34. Quinn BJ, Dallos M, Kitagawa H, et al., Inhibition of lung tumorigenesis by metformin is associated with decreased plasma IGF-I and diminished receptor tyrosine kinase signaling. Cancer Prev Res. 2013; 6: 801-810.
35. Hoshida Y, Fuchs BC, Tanabe KK,. Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges. Curr Cancer Drug Targets. 2012; 12: 1129-1159.
36. Alison MR,. Liver stem cells: implications for hepatocarcinogenesis. Stem Cell Rev. 2005; 1: 253-260.
37. Lee JS, Heo J, Libbrecht L, et al., A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med. 2006; 12: 410-416.
38. Yang XR, Xu Y, Yu B, et al., High expression levels of putative hepatic stem/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma. Gut. 2010; 59: 953-962.
39. Theise ND, Saxena R, Portmann BC, et al., The canals of Hering and hepatic stem cells in humans. Hepatology. 1999; 30: 1425-1433.
40. Hyogo H, Yamagishi S,. Advanced glycation end products (AGEs) and their involvement in liver disease. Curr Pharm Des. 2008; 14: 969-972.
41. Xia JR, Liu NF, Zhu NX,. Specific siRNA targeting the receptor for advanced glycation end products inhibits experimental hepatic fibrosis in rats. Int J Mol Sci. 2008; 9: 638-661.
42. Saito T, Chiba T, Yuki K, et al., Metformin, a diabetes drug, eliminates tumor-initiating hepatocellular carcinoma cells [serial online]. PLoS One. 2013; 8: e70010.
43. Zhu P, Davis M, Blackwelder AJ, et al., Metformin selectively targets tumor-initiating cells in ErbB2-overexpressing breast cancer models. Cancer Prev Res. 2014; 7: 199-210.
44. Mohammed A, Janakiram NB, Brewer M, et al., Antidiabetic drug metformin prevents progression of pancreatic cancer by targeting in part cancer stem cells and mTOR signaling. Transl Oncol. 2013; 6: 649-659.
45. Bao B, Wang Z, Ali S, et al., Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells. Cancer Prev Res. 2012; 5: 355-364.
46. Chiba T, Kita K, Zheng YW, et al., Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. 2006; 44: 240-251.
47. Yamashita T, Forgues M, Wang W, et al., EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res. 2008; 68: 1451-1461.
48. Yang ZF, Ho DW, Ng MN, et al., Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 2008; 13: 153-166.