Advertisement

Expression of fatty-acid-binding protein 5 in intrahepatic and extrahepatic cholangiocarcinoma: the possibility of different energy metabolisms in anatomical location

  • 83 Accesses

Abstract

The biliary tract cancer (BTC) covers a range of carcinomas, including intrahepatic cholangiocarcinoma (ICC), cholangiolocellular carcinoma (CoCC), perihilar cholangiocarcinoma (perihilar CC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC), defined according to the anatomical location. These adenocarcinomas mostly comprise biliary epithelial cell-derived malignant cells. In addition to anatomical differences, there are morphological and biological differences in BTC starting from embryonic development of the tissues extending to physiological differences. Fatty acid-binding proteins (FABPs) are closely associated with the energy metabolism. Using surgical specimens from 74 BTCs, we performed immunohistochemistry for FABP5 and its associated molecules, including peroxisome proliferator-activated receptor γ (PPARγ), PPARγ coactivator 1 (PGC-1), and estrogen-related receptor α (ERRα). We found that the expression patterns of small BTCs (ICC and CoCC) considerably differed from those of large BTCs (perihilar CC, ECC, and GBC). Expression of FABP5 and PGC-1 in large BTCs was high compared with those of small BTCs, but no difference in the expression of PPARγ and ERRα was observed. FABP5 appears to play a role in malignant progression in large BTCs. Small and large BTCs possess different energy metabolism systems owing to their different anatomical locations and course of carcinogenesis, although all BTCs originate from biliary epithelial cells.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2

References

  1. 1.

    Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M et al (2015) Genomic spectra of biliary tract cancer. Nat Genet 47(9):1003–1010

  2. 2.

    Cardinale V, Wang Y, Carpino G, Mendel G, Alpini G, Gaudio E et al (2012) The biliary tree—a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol 9(4):231–240

  3. 3.

    Vestentoft PS, Jelnes P, Hopkinson BM, Vainer B, Mollgard K, Quistorff B et al (2011) Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver. BMC Dev Biol 11:56

  4. 4.

    Sugiura H, Nakanuma Y (1989) Secretory component and immunoglobulins in the intrahepatic biliary tree and peribiliary gland in normal livers and hepatolithiasis. Gastroenterol Japonica 24(3):308–314

  5. 5.

    Tan CE, Vijayan V (2001) New clues for the developing human biliary system at the porta hepatis. J Hepatobiliary Pancreat Surg 8(4):295–302

  6. 6.

    Zhao DY, Lim KH (2017) Current biologics for treatment of biliary tract cancers. J Gastrointest Oncol 8(3):430–440

  7. 7.

    de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM (1999) Biliary tract cancers. N Engl J Med 341(18):1368–1378

  8. 8.

    Wistuba II, Gazdar AF (2004) Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer 4(9):695–706

  9. 9.

    Shen J, Goyal A, Sperling L (2012) The emerging epidemic of obesity, diabetes, and the metabolic syndrome in china. Cardiol Res Pract 2012:178675

  10. 10.

    Nettleton JA, Steffen LM, Mayer-Davis EJ, Jenny NS, Jiang R, Herrington DM et al (2006) Dietary patterns are associated with biochemical markers of inflammation and endothelial activation in the multi-ethnic study of atherosclerosis (MESA). Am J Clin Nutr 83(6):1369–1379

  11. 11.

    Barbaresko J, Koch M, Schulze MB, Nothlings U (2013) Dietary pattern analysis and biomarkers of low-grade inflammation: a systematic literature review. Nutr Rev 71(8):511–527

  12. 12.

    Lopez-Garcia E, Schulze MB, Fung TT, Meigs JB, Rifai N, Manson JE et al (2004) Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr 80(4):1029–1035

  13. 13.

    Esmaillzadeh A, Kimiagar M, Mehrabi Y, Azadbakht L, Hu FB, Willett WC (2007) Dietary patterns and markers of systemic inflammation among Iranian women. J Nutr 137(4):992–998

  14. 14.

    Giugliano D, Ceriello A, Esposito K (2006) The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol 48(4):677–685

  15. 15.

    Galland L (2010) Diet and inflammation. Nutr Clin Pract 25(6):634–640

  16. 16.

    Chrysohoou C, Panagiotakos DB, Pitsavos C, Das UN, Stefanadis C (2004) Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: the ATTICA study. J Am Coll Cardiol 44(1):152–158

  17. 17.

    Nanri A, Moore MA, Kono S (2007) Impact of C-reactive protein on disease risk and its relation to dietary factors. Asian Pac J Cancer Prev 8(2):167–177

  18. 18.

    Moerman CJ, Bueno de Mesquita HB, Runia S (1993) Dietary sugar intake in the aetiology of biliary tract cancer. Int J Epidemiol 22(2):207–214

  19. 19.

    Zhang XH, Andreotti G, Gao YT, Deng J, Liu E, Rashid A et al (2006) Tea drinking and the risk of biliary tract cancers and biliary stones: a population-based case-control study in Shanghai. China Int J Cancer 118(12):3089–3094

  20. 20.

    Park M, Song DY, Je Y, Lee JE (2014) Body mass index and biliary tract disease: a systematic review and meta-analysis of prospective studies. Prev Med 65:13–22

  21. 21.

    Wiseman M (2008) The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Proc Nutr Soc 67(3):253–256

  22. 22.

    Zimmerman AW, Veerkamp JH (2002) New insights into the structure and function of fatty acid-binding proteins. Cell Mol Life Sci 59(7):1096–1116

  23. 23.

    Zimmerman AW, Veerkamp JH (2001) Fatty-acid-binding proteins do not protect against induced cytotoxicity in a kidney cell model. Biochem J 360(Pt 1):159–165

  24. 24.

    Glatz JF, Storch J (2001) Unravelling the significance of cellular fatty acid-binding proteins. Curr Opin Lipidol 12(3):267–274

  25. 25.

    Madsen P, Rasmussen HH, Leffers H, Honore B, Celis JE (1992) Molecular cloning and expression of a novel keratinocyte protein (psoriasis-associated fatty acid-binding protein [PA-FABP]) that is highly up-regulated in psoriatic skin and that shares similarity to fatty acid-binding proteins. J Invest Dermatol 99(3):299–305

  26. 26.

    Haunerland NH, Spener F (2004) Fatty acid-binding proteins—insights from genetic manipulations. Prog Lipid Res 43(4):328–349

  27. 27.

    Forootan FS, Forootan SS, Malki MI, Chen D, Li G, Lin K et al (2014) The expression of C-FABP and PPARgamma and their prognostic significance in prostate cancer. Int J Oncol 44(1):265–275

  28. 28.

    Adamson J, Morgan EA, Beesley C, Mei Y, Foster CS, Fujii H et al (2003) High-level expression of cutaneous fatty acid-binding protein in prostatic carcinomas and its effect on tumorigenicity. Oncogene 22(18):2739–2749

  29. 29.

    Sinha P, Hutter G, Kottgen E, Dietel M, Schadendorf D, Lage H (1999) Increased expression of epidermal fatty acid binding protein, cofilin, and 14-3-3-sigma (stratifin) detected by two-dimensional gel electrophoresis, mass spectrometry and microsequencing of drug-resistant human adenocarcinoma of the pancreas. Electrophoresis 20(14):2952–2960

  30. 30.

    Giguere V (2002) To ERR in the estrogen pathway. Trends Endocrinol Metab 13(5):220–225

  31. 31.

    Schilling J, Kelly DP (2011) The PGC-1 cascade as a therapeutic target for heart failure. J Mol Cell Cardiol 51(4):578–583

  32. 32.

    Giguere V (2008) Transcriptional control of energy homeostasis by the estrogen-related receptors. Endocr Rev 29(6):677–696

  33. 33.

    Yang J, Williams RS, Kelly DP (2009) Bcl3 interacts cooperatively with peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha to coactivate nuclear receptors estrogen-related receptor alpha and PPARalpha. Mol Cell Biol 29(15):4091–4102

  34. 34.

    Kimura Y, Harada K, Nakanuma Y (2012) Pathologic significance of immunoglobulin G4-positive plasma cells in extrahepatic cholangiocarcinoma. Hum Pathol 43(12):2149–2156

  35. 35.

    Harada K, Sato Y, Ikeda H, Maylee H, Igarashi S, Okamura A et al (2012) Clinicopathologic study of mixed adenoneuroendocrine carcinomas of hepatobiliary organs. Virchows Arch 460(3):281–289

  36. 36.

    Harada K, Sato Y, Ikeda H, Hsu M, Igarashi S, Nakanuma Y (2013) Notch1-Hes1 signalling axis in the tumourigenesis of biliary neuroendocrine tumours. J Clin Pathol 66(5):386–391

  37. 37.

    Nakanuma Y, Jang KT, Fukushima N, Furukawa T, Hong SM, Kim H et al (2018) A statement by the Japan-Korea expert pathologists for future clinicopathological and molecular analyses toward consensus building of intraductal papillary neoplasm of the bile duct through several opinions at the present stage. J Hepatobiliary Pancreat Sci 25(3):181–187

  38. 38.

    Nguyen Canh H, Harada K (2016) Adult bile duct strictures: differentiating benign biliary stenosis from cholangiocarcinoma. Med Mol Morphol 49(4):189–202

  39. 39.

    Nakanuma Y, Harada K, Sasaki M, Sato Y (2014) Proposal of a new disease concept “biliary diseases with pancreatic counterparts”. Anatomical and pathological bases. Histol Histopathol 29(1):1–10

  40. 40.

    Ohata T, Yokoo H, Kamiyama T, Fukai M, Aiyama T, Hatanaka Y et al (2017) Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition. Cancer Med 6(5):1049–1061

  41. 41.

    Senga S, Kawaguchi K, Kobayashi N, Ando A, Fujii H (2018) A novel fatty acid-binding protein 5-estrogen-related receptor alpha signaling pathway promotes cell growth and energy metabolism in prostate cancer cells. Oncotarget 9(60):31753–31770

  42. 42.

    Forootan FS, Forootan SS, Gou X, Yang J, Liu B, Chen D et al (2016) Fatty acid activated PPARgamma promotes tumorigenicity of prostate cancer cells by up regulating VEGF via PPAR responsive elements of the promoter. Oncotarget 7(8):9322–9339

Download references

Author information

Correspondence to Kenichi Harada.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 16 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nakagawa, R., Hiep, N.C., Ouchi, H. et al. Expression of fatty-acid-binding protein 5 in intrahepatic and extrahepatic cholangiocarcinoma: the possibility of different energy metabolisms in anatomical location. Med Mol Morphol (2019). https://doi.org/10.1007/s00795-019-00230-9

Download citation

Keywords

  • Fatty-acid-binding protein 5
  • Biliary tract cancer
  • Extrahepatic cholangiocarcinoma
  • Intrahepatic cholangiocarcinoma
  • Energy metabolism