Integrin αvβ6 critically regulates hepatic progenitor cell function and promotes ductular reaction, fibrosis, and tumorigenesis

Hepatology

Volumn 63, Issue 1, 2016, Pages 217-232

  Peng, Zhen Wei ^a,b   Ikenaga, Naoki ^b   Liu, Susan B ^b   Sverdlov, Deanna Y ^b   Vaid, Kahini A ^b   Dixit, Richa ^b   Weinreb, Paul H ^c   Violette, Shelia ^c   Sheppard, Dean ^d   Schuppan, Detlef ^e   Popov, Yury ^b  

^a THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIVERSITY   (China)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BIOGEN   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTEGRIN; BETA6 INTEGRIN; TRANSFORMING GROWTH FACTOR BETA1; ALPHAVBETA6 INTEGRIN; INTEGRIN; TUMOR ANTIGEN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARCINOGENESIS; CELL EXPANSION; CELL FUNCTION; CONTROLLED STUDY; FEMALE; HEPATIC DUCT; LIVER CELL; LIVER FIBROSIS; LIVER TUMOR; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY MECHANISM; STEM CELL; ANIMAL; C57BL MOUSE; CHOLANGITIS, SCLEROSING; FIBROSIS; HUMAN; LIVER; LIVER CIRRHOSIS; LIVER NEOPLASMS; PATHOLOGY; PHYSIOLOGY;

ANIMALS; ANTIGENS, NEOPLASM; CARCINOGENESIS; CHOLANGITIS, SCLEROSING; FIBROSIS; HEPATOCYTES; HUMANS; INTEGRINS; LIVER; LIVER CIRRHOSIS; LIVER NEOPLASMS; MALE; MICE; MICE, INBRED C57BL; STEM CELLS;

EID: 84952638850     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.28274     Document Type: Article

References (50)

1. Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2009;51:660-678.
2. Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma. Lancet 2005;366:1303-1314.
3. Roskams T, Desmet V. Ductular reaction and its diagnostic significance. Semin Diagn Pathol 1998;15:259-269.
4. Lazaridis KN, Strazzabosco M, Larusso NF. The cholangiopathies: disorders of biliary epithelia. Gastroenterology 2004;127:1565-1577.
5. Popov Y, Schuppan D. Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies. Hepatology 2009;50:1294-1306.
6. Komuta M, Spee B, Vander Borght S, De Vos R, Verslype C, Aerts R, et al. Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin. Hepatology 2008;47:1544-1556.
7. Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 2006;12:410-416.
8. Jakubowski A, Ambrose C, Parr M, Lincecum JM, Wang MZ, Zheng TS, et al. TWEAK induces liver progenitor cell proliferation. J Clin Invest 2005;115:2330-2340.
9. Haybaeck J, Zeller N, Wolf MJ, Weber A, Wagner U, Kurrer MO, et al. A lymphotoxin-driven pathway to hepatocellular carcinoma. Cancer Cell 2009;16:295-308.
10. Breuss JM, Gallo J, DeLisser HM, Klimanskaya IV, Folkesson HG, Pittet JF, et al. Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. J Cell Sci 1995;108(Pt. 6):2241-2251.
11. Breuss JM, Gillett N, Lu L, Sheppard D, Pytela R. Restricted distribution of integrin beta 6 mRNA in primate epithelial tissues. J Histochem Cytochem 1993;41:1521-1527.
12. Shi M, Zhu J, Wang R, Chen X, Mi L, Walz T, et al. Latent TGF-beta structure and activation. Nature 2011;474:343-349.
13. Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, et al. The integrin alphavbeta6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 1999;96:319-328.
14. Popov Y, Patsenker E, Stickel F, Zaks J, Bhaskar KR, Niedobitek G, et al. Integrin alphavbeta6 is a marker of the progression of biliary and portal liver fibrosis and a novel target for antifibrotic therapies. J Hepatol 2008;48:453-464.
15. Patsenker E, Wilkens L, Banz V, Osterreicher CH, Weimann R, Eisele S, et al. The alphavbeta6 integrin is a highly specific immunohistochemical marker for cholangiocarcinoma. J Hepatol 2010;52:362-369.
16. Patsenker E, Popov Y, Stickel F, Jonczyk A, Goodman SL, Schuppan D. Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor-beta activation and retards biliary fibrosis progression. Gastroenterology 2008;135:660-670.
17. Wang B, Dolinski BM, Kikuchi N, Leone DR, Peters MG, Weinreb PH, et al. Role of alphavbeta6 integrin in acute biliary fibrosis. Hepatology 2007;46:1404-1412.
18. Sipos B, Hahn D, Carceller A, Piulats J, Hedderich J, Kalthoff H, et al. Immunohistochemical screening for beta6-integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up-regulation in pancreatic ductal adenocarcinomas in vivo and in vitro. Histopathology 2004;45:226-236.
19. Pi L, Robinson PM, Jorgensen M, Oh SH, Brown AR, Weinreb PH, et al. Connective tissue growth factor and integrin alphavbeta6: a new pair of regulators critical for ductular reaction and biliary fibrosis in mice. Hepatology 2015;61:678-691.
20. -/- mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro- and antifibrogenic genes. J Hepatol 2005;43:1045-1054.
21. Fickert P, Stoger U, Fuchsbichler A, Moustafa T, Marschall HU, Weiglein AH, et al. A new xenobiotic-induced mouse model of sclerosing cholangitis and biliary fibrosis. Am J Pathol 2007;171:525-536.
22. Kwong GA, von Maltzahn G, Murugappan G, Abudayyeh O, Mo S, Papayannopoulos IA, et al. Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease. Nat Biotechnol 2013;31:63-70.
23. Huang XZ, Wu JF, Cass D, Erle DJ, Corry D, Young SG, et al. Inactivation of the integrin beta6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin. J Cell Biol 1996;133:921-928.
24. Morris DG, Huang X, Kaminski N, Wang Y, Shapiro SD, Dolganov G, et al. Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Nature 2003;422:169-173.
25. Van Nieuwkerk CM, Elferink RP, Groen AK, Ottenhoff R, Tytgat GN, Dingemans KP, et al. Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene. Gastroenterology 1996;111:165-171.
26. Weinreb PH, Simon KJ, Rayhorn P, Yang WJ, Leone DR, Dolinski BM, et al. Function-blocking integrin alphavbeta6 monoclonal antibodies: distinct ligand-mimetic and nonligand-mimetic classes. J Biol Chem 2004;279:17875-17887.
27. Yoshida S, Ikenaga N, Liu SB, Peng ZW, Chung J, Sverdlov DY, et al. Extrahepatic platelet-derived growth factor-beta, delivered by platelets, promotes activation of hepatic stellate cells and biliary fibrosis in mice. Gastroenterology 2014;147:1378-1392.
28. Hu M, Yao J, Carroll DK, Weremowicz S, Chen H, Carrasco D, et al. Regulation of in situ to invasive breast carcinoma transition. Cancer Cell 2008;13:394-406.
29. Dorrell C, Erker L, Schug J, Kopp JL, Canaday PS, Fox AJ, et al. Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice. Genes Dev 2011;25:1193-1203.
30. Popov Y, Sverdlov DY, Sharma AK, Bhaskar KR, Li S, Freitag TL, et al. Tissue transglutaminase does not affect fibrotic matrix stability or regression of liver fibrosis in mice. Gastroenterology 2011;140:1642-1652.
31. Kuramitsu K, Sverdlov DY, Liu SB, Csizmadia E, Burkly L, Schuppan D, et al. Failure of fibrotic liver regeneration in mice is linked to a severe fibrogenic response driven by hepatic progenitor cell activation. Am J Pathol 2013;183:182-194.
32. -/- mouse model of sclerosing cholangitis with rapid fibrosis progression, early-onset portal hypertension, and liver cancer. Am J Pathol 2015;185:325-334.
33. + cells of normal and injured mouse liver. Development 2009;136:1951-1960.
34. Tarlow BD, Pelz C, Naugler WE, Wakefield L, Wilson EM, Finegold MJ, et al. Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes. Cell Stem Cell 2014;15:605-618.
35. Yanger K, Knigin D, Zong Y, Maggs L, Gu G, Akiyama H, et al. Adult hepatocytes are generated by self-duplication rather than stem cell differentiation. Cell Stem Cell 2014;15:340-349.
36. Cardinale V, Wang Y, Carpino G, Mendel G, Alpini G, Gaudio E, et al. The biliary tree-a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol 2012;9:231-240.
37. Itoh T, Miyajima A. Liver regeneration by stem/progenitor cells. Hepatology 2014;59:1617-1626.
38. Wang X, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M. The origin and liver repopulating capacity of murine oval cells. Proc Natl Acad Sci USA 2003;100(Suppl. 1):11881-11888.
39. Durnez A, Verslype C, Nevens F, Fevery J, Aerts R, Pirenne J, et al. The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathology 2006;49:138-151.
40. Roskams TA, Libbrecht L, Desmet VJ. Progenitor cells in diseased human liver. Semin Liver Dis 2003;23:385-396.
41. Clouston AD, Powell EE, Walsh MJ, Richardson MM, Demetris AJ, Jonsson JR. Fibrosis correlates with a ductular reaction in hepatitis C: roles of impaired replication, progenitor cells and steatosis. Hepatology 2005;41:809-818.
42. Richardson MM, Jonsson JR, Powell EE, Brunt EM, Neuschwander-Tetri BA, Bhathal PS, et al. Progressive fibrosis in nonalcoholic steatohepatitis: association with altered regeneration and a ductular reaction. Gastroenterology 2007;133:80-90.
43. Dixit RB, Chen A, Chen J, Sheppard D. Identification of a sequence within the integrin beta6 subunit cytoplasmic domain that is required to support the specific effect of alphavbeta6 on proliferation in three-dimensional culture. J Biol Chem 1996;271:25976-25980.
44. Nguyen LN, Furuya MH, Wolfraim LA, Nguyen AP, Holdren MS, Campbell JS, et al. Transforming growth factor-beta differentially regulates oval cell and hepatocyte proliferation. Hepatology 2007;45:31-41.
45. Mishra L, Derynck R, Mishra B. Transforming growth factor-beta signaling in stem cells and cancer. Science 2005;310:68-71.
46. Michalopoulos GK. The liver is a peculiar organ when it comes to stem cells. Am J Pathol 2014;184:1263-1267.
47. Lemaigre FP. Determining the fate of hepatic cells by lineage tracing: facts and pitfalls. Hepatology 2015;61:2100-2103.
48. Shin S, Walton G, Aoki R, Brondell K, Schug J, Fox A, et al. Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential. Genes Dev 2011;25:1185-1192.
49. + liver stem cells induced by Wnt-driven regeneration. Nature 2013;494:247-250.
50. Neef M, Ledermann M, Saegesser H, Schneider V, Widmer N, Decosterd LA, et al. Oral imatinib treatment reduces early fibrogenesis but does not prevent progression in the long term. J Hepatol 2006;44:167-175.