Fatty acid-binding protein 5 promotes cell proliferation and invasion in human intrahepatic cholangiocarcinoma

Jeong,Chi-Young; Hah,Young-Sool; Cho,Bok  Im; Lee,Seon  Min; Joo,Young-Tae; Jung,Eun-Jung; Jeong,Sang-Ho; Lee,Young-Joon; Choi,Sang-Kyung; Ha,Woo-Song; Park,Soon-Tae; Hong,Soon-Chan

doi:10.3892/or.2012.1922

Fatty acid-binding protein 5 promotes cell proliferation and invasion in human intrahepatic cholangiocarcinoma

Authors:
- Chi-Young Jeong
- Young-Sool Hah
- Bok Im Cho
- Seon Min Lee
- Young-Tae Joo
- Eun-Jung Jung
- Sang-Ho Jeong
- Young-Joon Lee
- Sang-Kyung Choi
- Woo-Song Ha
- Soon-Tae Park
- Soon-Chan Hong
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Affiliations: Department of Surgery, Gyeongsang National University School of Medicine, Institute of Health Sciences, Gyeongsang National University Hospital, Jinju 660-751, Republic of Korea, Clinical Research Institute, Gyeongsang National University Hospital, Jinju 660-751, Republic of Korea
Published online on: July 19, 2012 https://doi.org/10.3892/or.2012.1922
Pages: 1283-1292

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Abstract

Intrahepatic cholangiocarcinoma (ICC) is a rare primary malignant liver tumor with an extremely poor prognosis. Recently its incidence has increased, however, little attention has been directed to factors related to its molecular carcinogenesis, including oncogenes, tumor suppressor genes and cell cycle-related proteins. ICC is generally characterized by strong proliferation, invasion and early metastasis. These biological behaviors of ICC, with respect to the genetic and molecular aspects, remain to be clarified. In this study, we performed a proteomic analysis to identify the proteomic alterations associated with carcinogenesis of ICC. Protein expression profiles of sixteen cases of ICC were compared with those of adjacent non-involved bile duct tissue. Among the 151 protein spots that showed a statistically significant expression difference (P<0.05), there were 50 spots with significantly increased intensity (3-fold increase) and 17 spots with decreased intensity (3-fold decrease) in cancerous tissues. Of these, increased expression of fatty acid-binding protein 5 (FABP5) was further confirmed by western blot analysis and immunohistochemical analysis. Immunohistochemical analysis of FABP5 expression in tumor specimens obtained from 43 patients with mass-forming (MF) type ICC showed a positive correlation of FABP5 immunoreactivity with tumor size (P=0.047), lymph node metastasis (P=0.013), angioinvasion (P=0.032) and staging (P=0.007). In addition, silencing FABP5 with short hairpin RNA (shRNA) suppressed cell proliferation and invasiveness in HuCCT1 cells, and conversely, overexpression of FABP5 in FABP5-negative Hep3B cells increased cell proliferation and invasiveness. Our study shows that FABP5 is significantly overexpressed in ICC combined lymph node metastasis and is involved in cell proliferation and invasion in vitro. Our data suggest that FABP5 may be associated with tumor progression in ICC.

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1	Blechacz B and Gores GJ: Cholangiocarcinoma: advances in pathogenesis, diagnosis and treatment. Hepatology. 48:308–321. 2008. View Article : Google Scholar : PubMed/NCBI
2	Okabayashi T, Yamamoto J, Kosuge T, Shimada K, Yamasaki S, Takayama T and Makuuchi M: A new staging system for mass-forming intrahepatic cholangiocarcinoma. Cancer. 92:2374–2383. 2001. View Article : Google Scholar : PubMed/NCBI
3	Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, Cappellani A, Malfermoni G and Iacono C: Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection. World J Surg. 33:1247–1254. 2009. View Article : Google Scholar : PubMed/NCBI
4	Choi SB, Kim KS, Choi JY, Park SW, Choi JS, Lee WJ and Chung JB: The prognosis and survival outcome of intrahepatic cholangiocarcinoma following surgical resection: association of lymph node metastasis and lymph node dissection with survival. Ann Surg Oncol. 16:3048–3056. 2009. View Article : Google Scholar
5	Zimmerman AW and Veerkamp JH: New insights into the structure and function of fatty acid-binding proteins. Cell Mol Life Sci. 59:1096–1116. 2002. View Article : Google Scholar : PubMed/NCBI
6	Coe NR and Bernlohr DA: Physiological properties and functions of intracellular fatty acid-binding proteins. Biochim Biophys Acta. 1391:287–306. 1998. View Article : Google Scholar : PubMed/NCBI
7	Glatz JF and Storch J: Unravelling the significance of cellular fatty acid-binding proteins. Curr Opin Lipidol. 12:267–274. 2001. View Article : Google Scholar : PubMed/NCBI
8	Madsen P, Rasmussen HH, Leffers H, Honoré B and Celis JE: 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. 99:299–305. 1992.PubMed/NCBI
9	Haunerland NH and Spener F: Fatty acid-binding proteins - insights from genetic manipulations. Prog Lipid Res. 43:328–349. 2004. View Article : Google Scholar : PubMed/NCBI
10	Sinha P, Hütter G, Köttgen E, Dietel M, Schadendorf D and Lage H: 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. 20:2952–2960. 1999. View Article : Google Scholar
11	Ostergaard M, Rasmussen HH, Nielsen HV, Vorum H, Orntoft TF, Wolf H and Celis JE: Proteome profiling of bladder squamous cell carcinomas: identification of markers that define their degree of differentiation. Cancer Res. 57:4111–4117. 1997.PubMed/NCBI
12	Adamson J, Morgan EA, Beesley C, Mei Y, Foster CS, Fujii H, Rudland PS, Smith PH and Ke Y: High-level expression of cutaneous fatty acid-binding protein in prostatic carcinomas and its effect on tumorigenicity. Oncogene. 22:2739–2749. 2003. View Article : Google Scholar : PubMed/NCBI
13	Xu HE, Lambert MH and Montana VG: Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 3:397–403. 1999. View Article : Google Scholar : PubMed/NCBI
14	Morgan E, Kannan-Thulasiraman P and Noy N: Involvement of fatty acid binding protein 5 and PPARβ/δ in prostate cancer cell growth. PPAR Res. 2010:2346292010.
15	Jung EJ, Moon HG and Cho BI: Galectin-1 expression in cancer-associated stromal cells correlates tumor invasiveness and tumor progression in breast cancer. Int J Cancer. 120:2331–2338. 2007. View Article : Google Scholar : PubMed/NCBI
16	Landry F, Lombardo CR and Smith JW: A method for application of samples to matrix-assisted laser desorption ionization time-of-flight targets that enhances peptide detection. Anal Biochem. 279:1–8. 2000. View Article : Google Scholar : PubMed/NCBI
17	Yates JR: Database searching using mass spectrometry data. Electrophoresis. 19:893–900. 1998. View Article : Google Scholar : PubMed/NCBI
18	Hsu SM, Raine L and Fanger H: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 29:577–580. 1981. View Article : Google Scholar
19	Fang LY, Wong TY, Chiang WF and Chen YL: Fatty-acid-binding protein 5 promotes cell proliferation and invasion in oral squamous cell carcinoma. J Oral Pathol Med. 39:342–348. 2010. View Article : Google Scholar : PubMed/NCBI
20	Sirica AE: Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy. Hepatology. 41:5–15. 2005. View Article : Google Scholar : PubMed/NCBI
21	Shimonishi T, Sasaki M and Nakanuma Y: Precancerous lesions of intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg. 7:542–550. 2000. View Article : Google Scholar
22	Kawase H, Fujii K, Miyamoto M, Kubota KC, Hirano S, Kondo S and Inagaki F: Differential LC-MS-based proteomics of surgical human cholangiocarcinoma tissues. J Proteome Res. 8:4092–4103. 2009. View Article : Google Scholar : PubMed/NCBI
23	Srisomsap C, Sawangareetrakul P, Subhasitanont P, Panichakul T, Keeratichamroen S, Lirdprapamongkol K, Chokchaichamnankit D, Sirisinha S and Svasti J: Proteomic analysis of cholangiocarcinoma cell line. Proteomics. 4:1135–1144. 2004. View Article : Google Scholar : PubMed/NCBI
24	Jing C, Beesley C, Foster CS, Chen H, Rudland PS, West DC, Fujii H, Smith PH and Ke Y: Human cutaneous fatty acid-binding protein induces metastasis by up-regulating the expression of vascular endothelial growth factor gene in rat Rama 37 model cells. Cancer Res. 61:4357–4364. 2001.
25	Fujii K, Kondo T, Yokoo H, Yamada T, Iwatsuki K and Hirohashi S: Proteomic study of human hepatocellular carcinoma using two-dimensional difference gel electrophoresis with saturation cysteine dye. Proteomics. 5:1411–1422. 2005. View Article : Google Scholar : PubMed/NCBI
26	Glatz JFC, Schaap FG, Binas B, Bonen A, van der Vusse GJ and Luiken J: Cytoplasmic fatty acid-binding protein facilitates fatty acid utilization by skeletal muscle. Acta Physiol Scand. 178:367–371. 2003. View Article : Google Scholar : PubMed/NCBI
27	Schroeder F, Petrescu AD, Huang H, Atshaves BP, McIntosh AL, Martin GG, Hostetler HA, Vespa A, Landrock D and Landrock KK: Role of fatty acid binding proteins and long chain fatty acids in modulating nuclear receptors and gene transcription. Lipids. 43:1–17. 2008. View Article : Google Scholar : PubMed/NCBI
28	Desvergne B and Wahli W: Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 20:649–688. 1999.PubMed/NCBI
29	Lim K, Han C, Xu L, Isse K, Demetris AJ and Wu T: Cyclooxygenase-2-derived prostaglandin E2 activates beta-catenin in human cholangiocarcinoma cells: evidence for inhibition of these signaling pathways by omega 3 polyunsaturated fatty acids. Cancer Res. 68:553–560. 2008. View Article : Google Scholar
30	Wu T: Cyclooxygenase-2 and prostaglandin signaling in cholangiocarcinoma. Biochim Biophys Acta. 1755:135–150. 2005.PubMed/NCBI
31	Xu L, Han C and Wu T: A novel positive feedback loop between peroxisome proliferator-activated receptor-delta and prostaglandin E2 signaling pathways for human cholangiocarcinoma cell growth. J Biol Chem. 281:33982–33996. 2006. View Article : Google Scholar