Differential expression of fatty acid‑binding proteins and pathological implications in the progression of tongue carcinoma

Ohyama,Yoshito; Kawamoto,Yukihiro; Chiba,Tadashige; Kikuchi,Kentaro; Sakashita,Hideaki; Imai,Kazushi

doi:10.3892/mco.2013.198

Differential expression of fatty acid‑binding proteins and pathological implications in the progression of tongue carcinoma

Authors:
- Yoshito Ohyama
- Yukihiro Kawamoto
- Tadashige Chiba
- Kentaro Kikuchi
- Hideaki Sakashita
- Kazushi Imai
View Affiliations

Affiliations: Division of Oral and Maxillofacial Surgery 2, Department of Diagnostic and Therapeutic Science, School of Dentistry, Meikai University, Sakado, Saitama 3500283, Japan, Department of Biochemistry, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo 1028159, Japan, Division of Pathology, Department of Diagnostic and Therapeutic Science, School of Dentistry, Meikai University, Sakado, Saitama 3500283, Japan
Published online on: October 3, 2013 https://doi.org/10.3892/mco.2013.198
Pages: 19-25

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Tongue carcinomas are common malignancies of the oral cavity. Understanding the molecular mechanisms behind the disease progression is a prerequisite for improving patient prognosis. Fatty acid‑binding proteins (FABPs) are cytoplasmic lipid chaperones that affect cellular organization and energy production. Although their aberrant expression is involved in carcinoma progression, its role in the pathology of tongue carcinomas remains unclear. In the present study, the immunohistochemical expression of FABP4 and FABP5 in tongue carcinomas (n=58) and its involvement in the clinicopathological parameters were examined. Normal tongue epithelial cells expressed FABP5, an epidermal‑type FABP, but not FABP4, an adipocyte‑type FABP. The cytoplasmic staining of FABP5 was increased in carcinomas with advanced T‑stage (P<0.05) and clinical stage (P<0.05). Ectopic expression of FABP4 was detected in almost all carcinomas, although its role in disease progression remains undetermined. Upregulation of FABP5 in the wounded skin of genetically normal mice indicated that microenvironmental tissue factors induce FABP5 expression. The results of the present study demonstrated the aberrant expression of FABP4 and FABP5 in tongue carcinomas and suggested the involvement of FABP5 in disease progression.

View Figures

View References

1.	Regezi JA, Sciubba JJ and Jordan RCK: Oral Pathology: Clinical Pathologic Correlations. 5th edition. Saunders-Elsevier; Philadelphia, PA: pp. 552–556. 2008
2.	Ariyoshi Y, Shimahara M, Omura K, Yamamoto E, Mizuki H, Chiba H, Imai Y, Fujita S, Shinohara M and Seto K; Japanese Society of Oral and Maxillofacial Surgeons: Epidemiological study of malignant tumors in the oral and maxillofacial region: survey of member institutions of the Japanese Society of Oral and Maxillofacial Surgeons, 2002. Int J Clin Oncol. 13:220–228. 2008. View Article : Google Scholar : PubMed/NCBI
3.	Choi S and Myers JN: Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res. 87:14–32. 2008. View Article : Google Scholar : PubMed/NCBI
4.	Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
5.	Cairns RA, Harris IS and Mak TW: Regulation of cancer cell metabolism. Nat Rev Cancer. 11:85–95. 2011. View Article : Google Scholar
6.	Fuchs E: Epidermal differentiation: the bare essentials. J Cell Biol. 111:2807–2814. 1990. View Article : Google Scholar : PubMed/NCBI
7.	Ward PS and Thompson CB: Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell. 21:297–308. 2012. View Article : Google Scholar : PubMed/NCBI
8.	Furuhashi M and Hotamisligil GS: Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 7:489–503. 2008. View Article : Google Scholar : PubMed/NCBI
9.	Smathers RL and Petersen DR: The human fatty-acid binding protein family: evolutionary divergences and functions. Hum Genomics. 5:170–191. 2011. View Article : Google Scholar : PubMed/NCBI
10.	Siegenthaler G, Hotz R, Chatellard-Gruaz D, Jaconi S and Saurat JH: Characterization and expression of a novel human fatty acid-binding protein: the epidermal type (E-FABP). Biochem Biophys Res Commun. 190:482–487. 1993. View Article : Google Scholar : PubMed/NCBI
11.	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
12.	Melle C, Ernst G, Winkler R, Schimmel B, Klussmann JP, Wittekindt C, Guntinas-Lichius O and von Eggeling F: Proteomic analysis of human papillomavirus-related oral squamous cell carcinoma: identification of thioredoxin and epidermal-fatty acid binding protein as upregulated protein markers in microdissected tumor tissue. Proteomics. 9:2193–2201. 2009. View Article : Google Scholar
13.	Uma RS, Naresh KN, D’Cruz AK, Mulherkar R and Borges AM: Metastasis of squamous cell carcinoma of the oral tongue is associated with down-regulation of epidermal fatty acid binding protein (E-FABP). Oral Oncol. 43:27–32. 2007. View Article : Google Scholar : PubMed/NCBI
14.	Hashimoto T, Kusakabe T, Sugino T, Fukuda T, Watanabe K, Sato Y, Nashimoto A, Honma K, Kimura H, Fujii H and Suzuki T: Expression of heart-type fatty acid-binding protein in human gastric carcinoma and its association with tumor aggressiveness, metastasis and poor prognosis. Pathobiology. 71:267–273. 2004. View Article : Google Scholar : PubMed/NCBI
15.	Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Millis GB, Hotamisligil GS, et al: Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 17:1498–1503. 2011. View Article : Google Scholar : PubMed/NCBI
16.	Celis JE, Ostergaard M, Basse B, Celis A, Lauridsen JB, Ratz GP, Andersen I, Hein B, Wolf H, Orntoft TF and Rasmussen HH: Loss of adipocyte-type fatty acid binding protein and other protein biomarkers is associated with progression of human bladder transitional cell carcinomas. Cancer Res. 56:4782–4790. 1996.
17.	Boiteux G, Lascombe I, Roche E, Plissonnier ML, Clairotte A, Bittard H and Fauconnet S: A-FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells. Int J Cancer. 124:1820–1828. 2009. View Article : Google Scholar : PubMed/NCBI
18.	Hammamieh R, Chakraborty N, Barmada M, Das R and Jett M: Expression patterns of fatty acid binding proteins in breast cancer cells. J Exp Ther Oncol. 5:133–143. 2005.PubMed/NCBI
19.	Okuse T, Chiba T, Katsuumi I and Imai K: Differential expression and localization of WNTs in an animal model of skin wound healing. Wound Repair Regen. 13:491–497. 2005. View Article : Google Scholar : PubMed/NCBI
20.	McCluggage WG, Connolly LE, McBride HA, Kalloger S and Gilks CB: HMGA2 is commonly expressed in uterine serous carcinomas and is a useful adjunct to diagnosis. Histopathology. 60:547–553. 2012. View Article : Google Scholar : PubMed/NCBI
21.	Masouye I, Hagens G, Van Kuppevelt TH, Madsen P, Saurat JH, Veerkamp JH, Pepper MS and Siegenthaler G: Endothelial cells of the human microvasculature express epidermal fatty acid-binding protein. Circ Res. 81:297–303. 1997. View Article : Google Scholar : PubMed/NCBI
22.	Kusakari Y, Ogawa E, Owada Y, Kitanaka N, Watanabe H, Kimura M, Tagami H, Kondo H, Aiba S and Okuyama R: Decreased keratinocyte motility in skin wound on mice lacking the epidermal fatty acid binding protein gene. Mol Cell Biochem. 284:183–188. 2006. View Article : Google Scholar : PubMed/NCBI
23.	Han J, Kioi M, Chu WS, Kasperbauer JL, Strome SE and Puri RK: Identification of potential therapeutic targets in human head and neck squamous cell carcinoma. Head Neck Oncol. 1:272009. View Article : Google Scholar : PubMed/NCBI
24.	Chi C and Trinkaus-Randall V: New insights in wound response and repair of epithelium. J Cell Physiol. 228:925–929. 2013. View Article : Google Scholar : PubMed/NCBI
25.	Martin P: Wound healing - aiming for perfect skin regeneration. Science. 276:75–81. 1997. View Article : Google Scholar : PubMed/NCBI
26.	Singer AJ and Clark RA: Cutaneous wound healing. N Engl J Med. 341:738–746. 1999. View Article : Google Scholar : PubMed/NCBI
27.	Ogawa E, Owada Y, Ikawa S, Adachi Y, Egawa T, Nemoto K, Suzuki K, Hishinuma T, Kawashima H, Kondo H, et al: Epidermal FABP (FABP5) regulates keratinocyte differentiation by 13(S)-HODE-mediated activation of the NF-κB signaling pathway. J Invest Dermatol. 131:604–612. 2011.PubMed/NCBI
28.	Hagens G, Masouye I, Augsburger E, Hotz R, Saurat JH and Siegenthaler G: Calcium-binding protein S100A7 and epidermal-type fatty acid-binding protein are associated in the cytosol of human keratinocytes. Biochem J. 339:419–427. 1999. View Article : Google Scholar : PubMed/NCBI
29.	Dallaglio K, Marconi A, Truzzi F, Lotti R, Palazzo E, Petrachi T, Saltari A, Coppini M and Pincelli C: E-FABP induces differentiation in normal human keratinocytes and modulates the differentiation process in psoriatic keratinocytes in vitro. Exp Dermatol. 22:255–261. 2013. View Article : Google Scholar : PubMed/NCBI
30.	Gandarillas A: The mysterious human epidermal cell cycle, or an oncogene-induced differentiation checkpoint. Cell Cycle. 11:4507–4516. 2012. View Article : Google Scholar : PubMed/NCBI
31.	Ashida S, Orloff MS, Bebek G, Zhang L, Zheng P, Peehl CM and Eng C: Integrated analysis reveals critical genomic regions in prostate tumor microenvironment associated with clinicopathologic phenotypes. Clin Cancer Res. 18:1578–1587. 2012. View Article : Google Scholar
32.	Shirakata Y, Kimura R, Nanba D, Iwamoto R, Tokumaru S, Morimoto C, Yokota K, Nakamura M, Sayama K, Mekada E, et al: Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing. J Cell Sci. 118:2363–2370. 2005. View Article : Google Scholar : PubMed/NCBI
33.	Kannan-Thulasiraman P, Seachrist DD, Mahabeleshwar GH, Jain MK and Noy N: Fatty acid-binding protein 5 and PPAR-β/δ are critical mediators of epidermal growth factor receptor-induced carcinoma cell growth. J Biol Chem. 285:19106–19115. 2010.
34.	Uraguchi M, Morikawa M, Shirakawa M, Sanada K and Imai K: Activation of WNT family expression and signaling in squamous cell carcinomas of the oral cavity. J Dent Res. 83:327–332. 2004. View Article : Google Scholar : PubMed/NCBI
35.	Bielefeld KA, Amini-Nik S and Alman BA: Cutaneous wound healing: recruiting developmental pathways for regeneration. Cell Mol Life Sci. 70:2059–2081. 2013. View Article : Google Scholar : PubMed/NCBI
36.	Collins CA and Watt FM: Dynamic regulation of retinoic acid-binding proteins in developing, adult and neoplastic skin reveals roles for beta-catenin and Notch signalling. Dev Biol. 324:55–67. 2008. View Article : Google Scholar : PubMed/NCBI
37.	Knoferle J, Ramljak S, Koch JC, Tonges L, Asif AR, Michel U, Wouters FS, Heermann S, Krieglstein K, Zerr I, et al: TGF-beta 1 enhances neurite outgrowth via regulation of proteasome function and EFABP. Neurobiol Dis. 38:395–404. 2010. View Article : Google Scholar : PubMed/NCBI
38.	Imai K, Hiramatsu A, Fukushima D, Pierschbacher PD and Okada Y: Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-beta1 release. Biochem J. 322:809–814. 1997.PubMed/NCBI
39.	Chiba T, Maeda G, Kawashiri S, Kato K and Imai K: Epigenetic loss of mucosa-associated lymphoid tissue 1 expression in patients with oral carcinomas. Cancer Res. 69:7216–7223. 2009. View Article : Google Scholar : PubMed/NCBI
40.	Ohyama Y, Kawamoto Y, Chiba T, Maeda G, Sakashita H and Imai K: Inhibition of TGF-β and EGF pathway gene expression and migration of oral carcinoma cells by mucosa-associated lymphoid tissue 1. Br J Cancer. 109:207–214. 2013.
41.	Tuncman G, Erbay E, Hom X, De Vivo I, Campos H, Rimm EB and Hotamisligil GS: A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease. Proc Natl Acad Sci USA. 103:6970–6975. 2006. View Article : Google Scholar : PubMed/NCBI
42.	Theocharis S, Klijanienko J, Giaginis C, Rodriguez J, Jouffroy T, Girod A, Point D, Tsourouflis G and Satre-Garau X: Peroxisome proliferator-activated receptor-γ in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival. J Cancer Res Clin Oncol. 137:251–259. 2011.
43.	Yoshida K, Hirose Y, Tanaka T, Yamada Y, Kuno T, Kohno H, Katayama H, Qiao Z, Sakata K, Sugie S, et al: Inhibitory effects of troglitazone, a peroxisome proliferator-activated receptor γ ligand, in rat tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide. Cancer Sci. 94:365–371. 2003.
44.	Kawamoto Y, Ohyama Y, Chiba T, Yagishita H, Sakashita H and Imai K: Proteomic identification of keratin alterations with enhanced proliferation of oral carcinoma cells by loos of mucosa-associated lymphoid tissue 1 expression. Int J Oncol. 43:729–736. 2013.