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Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

Authors: Angelika Tölle, Monika Jung, Michael Lein, Manfred Johannsen, Kurt Miller, Holger Moch, Klaus Jung, Glen Kristiansen

Published in: BMC Cancer | Issue 1/2009

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Abstract

Background

Renal cell carcinoma (RCC) is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP) are involved in the intracellular transport of fatty acids (FA). We examined the level of brain-type (B) and liver-type (L) FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma.

Methods

Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative RT-PCR, immunohistochemistry and western blotting were used to determine B- and L-FABP in tumor and normal tissues. The tissue microarray (TMA) contained 272 clinico-pathologically characterized renal cell carcinomas of the clear cell, papillary and chromophobe subtype. SPSS 17.0 was used to apply crosstables (χ2-test), correlations and survival analyses.

Results

B-FABP mRNA was significantly up-regulated in renal cell carcinoma. In normal tissue B-FABP mRNA was very low or often not detectable. RCC with a high tumor grading (G3 + G4) showed significantly lower B-FABP mRNA compared with those with a low grading (G1 + G2). Western blotting analysis detected B-FABP in 78% of the cases with a very strong band but in the corresponding normal tissue it was weak or not detectable. L-FABP showed an inverse relationship for mRNA quantification and western blotting. A strong B-FABP staining was present in 52% of the tumor tissues contained in the TMA. In normal renal tissue, L-FABP showed a moderate to strong immunoreactivity in proximal tubuli. L-FABP was expressed at lower rates compared with the normal tissues in 30.5% of all tumors. There was no correlation between patient survival times and the staining intensity of both FABPs.

Conclusion

While B-FABP is over expressed in renal cell carcinoma in comparison to normal renal tissues L-FABP appears to be reduced in tumor tissue. Although the expression behavior was not related to the survival outcome of the RCC patients, it can be assumed that these changes indicate fundamental alterations in the fatty metabolism in the RCC carcinogenesis. Further studies should identify the role of both FABPs in carcinogenesis, progression and with regard to a potential target in RCC.
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Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al: Cancer statistics, 2008. CA Cancer J Clin. 2008, 58: 71-96. 10.3322/CA.2007.0010.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al: Cancer statistics, 2008. CA Cancer J Clin. 2008, 58: 71-96. 10.3322/CA.2007.0010.CrossRefPubMed
2.
go back to reference Schrader AJ, Varga Z, Hegele A, Pfoertner S, Olbert P, Hofmann R: Second-line strategies for metastatic renal cell carcinoma: classics and novel approaches. J Cancer Res Clin Oncol. 2006, 132: 137-149. 10.1007/s00432-005-0058-4.CrossRefPubMed Schrader AJ, Varga Z, Hegele A, Pfoertner S, Olbert P, Hofmann R: Second-line strategies for metastatic renal cell carcinoma: classics and novel approaches. J Cancer Res Clin Oncol. 2006, 132: 137-149. 10.1007/s00432-005-0058-4.CrossRefPubMed
3.
go back to reference Gesellschaft der epidemiologischen Krebsregister in Deutschland. 6. 2008, Auflage, Robert Koch Institute, Berlin Gesellschaft der epidemiologischen Krebsregister in Deutschland. 6. 2008, Auflage, Robert Koch Institute, Berlin
4.
go back to reference Escudier B: Advanced renal cell carcinoma: current and emerging management strategies. Drugs. 2007, 67: 1257-1264. 10.2165/00003495-200767090-00002.CrossRefPubMed Escudier B: Advanced renal cell carcinoma: current and emerging management strategies. Drugs. 2007, 67: 1257-1264. 10.2165/00003495-200767090-00002.CrossRefPubMed
5.
go back to reference Pittoggi C, Martis G, Mastrangeli G, Mastrangeli B, Spadafora C: In vitro evidence for a new therapeutic approach in renal cell carcinoma. Int Braz J Urol. 2008, 34: 492-502. 10.1590/S1677-55382008000400012.CrossRefPubMed Pittoggi C, Martis G, Mastrangeli G, Mastrangeli B, Spadafora C: In vitro evidence for a new therapeutic approach in renal cell carcinoma. Int Braz J Urol. 2008, 34: 492-502. 10.1590/S1677-55382008000400012.CrossRefPubMed
6.
go back to reference Glatz JF, van Nieuwenhoven FA, Luiken JJ, Schaap FG, Vusse van der GJ: Role of membrane-associated and cytoplasmic fatty acid-binding proteins in cellular fatty acid metabolism. Prostaglandins Leukot Essent Fatty Acids. 1997, 57: 373-378. 10.1016/S0952-3278(97)90413-0.CrossRefPubMed Glatz JF, van Nieuwenhoven FA, Luiken JJ, Schaap FG, Vusse van der GJ: Role of membrane-associated and cytoplasmic fatty acid-binding proteins in cellular fatty acid metabolism. Prostaglandins Leukot Essent Fatty Acids. 1997, 57: 373-378. 10.1016/S0952-3278(97)90413-0.CrossRefPubMed
7.
go back to reference Furuhashi M, Hotamisligil GS: Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 2008, 7: 489-503. 10.1038/nrd2589.CrossRefPubMedPubMedCentral Furuhashi M, Hotamisligil GS: Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 2008, 7: 489-503. 10.1038/nrd2589.CrossRefPubMedPubMedCentral
8.
go back to reference Hammamieh R, Chakraborty N, Das R, Jett M: Molecular impacts of antisense complementary to the liver fatty acid binding protein (FABP) mRNA in DU 145 prostate cancer cells in vitro. J Exp Ther Oncol. 2004, 4: 195-202.PubMed Hammamieh R, Chakraborty N, Das R, Jett M: Molecular impacts of antisense complementary to the liver fatty acid binding protein (FABP) mRNA in DU 145 prostate cancer cells in vitro. J Exp Ther Oncol. 2004, 4: 195-202.PubMed
9.
go back to reference Hammamieh R, Chakraborty N, Barmada M, Das R, Jett M: Expression patterns of fatty acid binding proteins in breast cancer cells. J Exp Ther Oncol. 2005, 5: 133-143.PubMed Hammamieh R, Chakraborty N, Barmada M, Das R, Jett M: Expression patterns of fatty acid binding proteins in breast cancer cells. J Exp Ther Oncol. 2005, 5: 133-143.PubMed
10.
go back to reference Ohlsson G, Moreira JM, Gromov P, Sauter G, Celis JE: Loss of expression of the adipocyte-type fatty acid-binding protein (A-FABP) is associated with progression of human urothelial carcinomas. Mol Cell Proteomics. 2005, 4: 570-581. 10.1074/mcp.M500017-MCP200.CrossRefPubMed Ohlsson G, Moreira JM, Gromov P, Sauter G, Celis JE: Loss of expression of the adipocyte-type fatty acid-binding protein (A-FABP) is associated with progression of human urothelial carcinomas. Mol Cell Proteomics. 2005, 4: 570-581. 10.1074/mcp.M500017-MCP200.CrossRefPubMed
11.
go back to reference Mita R, Coles JE, Glubrecht DD, Sung R, Sun X, Godbout R: B-FABP-expressing radial glial cells: the malignant glioma cell of origin?. Neoplasia. 2007, 9: 734-744. 10.1593/neo.07439.CrossRefPubMedPubMedCentral Mita R, Coles JE, Glubrecht DD, Sung R, Sun X, Godbout R: B-FABP-expressing radial glial cells: the malignant glioma cell of origin?. Neoplasia. 2007, 9: 734-744. 10.1593/neo.07439.CrossRefPubMedPubMedCentral
12.
go back to reference Jones J, Otu H, Spentzos D, Kolia S, Inan M, Beecken WD, et al: Gene signatures of progression and metastasis in renal cell cancer. Clin Cancer Res. 2005, 11: 5730-5739. 10.1158/1078-0432.CCR-04-2225.CrossRefPubMed Jones J, Otu H, Spentzos D, Kolia S, Inan M, Beecken WD, et al: Gene signatures of progression and metastasis in renal cell cancer. Clin Cancer Res. 2005, 11: 5730-5739. 10.1158/1078-0432.CCR-04-2225.CrossRefPubMed
13.
go back to reference Seliger B, Lichtenfels R, Atkins D, Bukur J, Halder T, Kersten M, et al: Identification of fatty acid binding proteins as markers associated with the initiation and/or progression of renal cell carcinoma. Proteomics. 2005, 5: 2631-2640. 10.1002/pmic.200401264.CrossRefPubMed Seliger B, Lichtenfels R, Atkins D, Bukur J, Halder T, Kersten M, et al: Identification of fatty acid binding proteins as markers associated with the initiation and/or progression of renal cell carcinoma. Proteomics. 2005, 5: 2631-2640. 10.1002/pmic.200401264.CrossRefPubMed
14.
go back to reference Maatman RG, van Kuppevelt TH, Veerkamp JH: Two types of fatty acid-binding protein in human kidney. Isolation, characterization and localization. Biochem J. 1991, 273 (Pt 3): 759-766.CrossRefPubMedPubMedCentral Maatman RG, van Kuppevelt TH, Veerkamp JH: Two types of fatty acid-binding protein in human kidney. Isolation, characterization and localization. Biochem J. 1991, 273 (Pt 3): 759-766.CrossRefPubMedPubMedCentral
15.
go back to reference Kimura H, Fujii H, Suzuki S, Ono T, Arakawa M, Gejyo F: Lipid-binding proteins in rat and human kidney. Kidney Int Suppl. 1999, 71: S159-S162. 10.1046/j.1523-1755.1999.07141.x.CrossRefPubMed Kimura H, Fujii H, Suzuki S, Ono T, Arakawa M, Gejyo F: Lipid-binding proteins in rat and human kidney. Kidney Int Suppl. 1999, 71: S159-S162. 10.1046/j.1523-1755.1999.07141.x.CrossRefPubMed
16.
go back to reference Lopez-Beltran A, Scarpelli M, Montironi R, Kirkali Z: 2004 WHO classification of the renal tumors of the adults. Eur Urol. 2006, 49: 798-805. 10.1016/j.eururo.2005.11.035.CrossRefPubMed Lopez-Beltran A, Scarpelli M, Montironi R, Kirkali Z: 2004 WHO classification of the renal tumors of the adults. Eur Urol. 2006, 49: 798-805. 10.1016/j.eururo.2005.11.035.CrossRefPubMed
17.
go back to reference Jung M, Ramankulov A, Roigas J, Johannsen M, Ringsdorf M, Kristiansen G, et al: In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR. BMC Mol Biol. 2007, 8: 47-10.1186/1471-2199-8-47.CrossRefPubMedPubMedCentral Jung M, Ramankulov A, Roigas J, Johannsen M, Ringsdorf M, Kristiansen G, et al: In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR. BMC Mol Biol. 2007, 8: 47-10.1186/1471-2199-8-47.CrossRefPubMedPubMedCentral
18.
go back to reference Fritzsche FR, Jung M, Tolle A, Wild P, Hartmann A, Wassermann K, et al: ADAM9 Expression is a Significant and Independent Prognostic Marker of PSA Relapse in Prostate Cancer. Eur Urol. 2008, 54: 1097-1106. 10.1016/j.eururo.2007.11.034.CrossRefPubMed Fritzsche FR, Jung M, Tolle A, Wild P, Hartmann A, Wassermann K, et al: ADAM9 Expression is a Significant and Independent Prognostic Marker of PSA Relapse in Prostate Cancer. Eur Urol. 2008, 54: 1097-1106. 10.1016/j.eururo.2007.11.034.CrossRefPubMed
19.
go back to reference Patard JJ, Pantuck AJ, Crepel M, Lam JS, Bellec L, Albouy B, et al: Morbidity and clinical outcome of nephron-sparing surgery in relation to tumour size and indication. Eur Urol. 2007, 52: 148-154. 10.1016/j.eururo.2007.01.039.CrossRefPubMed Patard JJ, Pantuck AJ, Crepel M, Lam JS, Bellec L, Albouy B, et al: Morbidity and clinical outcome of nephron-sparing surgery in relation to tumour size and indication. Eur Urol. 2007, 52: 148-154. 10.1016/j.eururo.2007.01.039.CrossRefPubMed
20.
go back to reference Nikiforova NV, Kirpatovsky VI, Darenkov AF, Chumakov AM, Sevrukov EA, Darenkov SP: Liposoluble vitamins E and A in human renal cortex and renal cell carcinomas. Nephron. 1995, 69: 449-453. 10.1159/000188518.CrossRefPubMed Nikiforova NV, Kirpatovsky VI, Darenkov AF, Chumakov AM, Sevrukov EA, Darenkov SP: Liposoluble vitamins E and A in human renal cortex and renal cell carcinomas. Nephron. 1995, 69: 449-453. 10.1159/000188518.CrossRefPubMed
21.
go back to reference Horiguchi A, Asano T, Asano T, Ito K, Sumitomo M, Hayakawa M: Fatty acid synthase over expression is an indicator of tumor aggressiveness and poor prognosis in renal cell carcinoma. J Urol. 2008, 180: 1137-1140. 10.1016/j.juro.2008.04.135.CrossRefPubMed Horiguchi A, Asano T, Asano T, Ito K, Sumitomo M, Hayakawa M: Fatty acid synthase over expression is an indicator of tumor aggressiveness and poor prognosis in renal cell carcinoma. J Urol. 2008, 180: 1137-1140. 10.1016/j.juro.2008.04.135.CrossRefPubMed
22.
go back to reference Glatz JF, Storch J: Unravelling the significance of cellular fatty acid-binding proteins. Curr Opin Lipidol. 2001, 12: 267-274. 10.1097/00041433-200106000-00005.CrossRefPubMed Glatz JF, Storch J: Unravelling the significance of cellular fatty acid-binding proteins. Curr Opin Lipidol. 2001, 12: 267-274. 10.1097/00041433-200106000-00005.CrossRefPubMed
23.
go back to reference Glatz JFC, Voort van der D, Hermens WT: Fatty Acid-binding Protein as the Earliest Available Plasma Marker of Acute Myocardial Injury. Clinical Ligand Assay. 2002, 25: 167-177. Glatz JFC, Voort van der D, Hermens WT: Fatty Acid-binding Protein as the Earliest Available Plasma Marker of Acute Myocardial Injury. Clinical Ligand Assay. 2002, 25: 167-177.
24.
go back to reference Pelsers MM, Hermens WT, Glatz JF: Fatty acid-binding proteins as plasma markers of tissue injury. Clin Chim Acta. 2005, 352: 15-35. 10.1016/j.cccn.2004.09.001.CrossRefPubMed Pelsers MM, Hermens WT, Glatz JF: Fatty acid-binding proteins as plasma markers of tissue injury. Clin Chim Acta. 2005, 352: 15-35. 10.1016/j.cccn.2004.09.001.CrossRefPubMed
25.
go back to reference Guthmann F, Schachtrup C, Tolle A, Wissel H, Binas B, Kondo H, et al: Phenotype of palmitic acid transport and of signalling in alveolar type II cells from E/H-FABP double-knockout mice: contribution of caveolin-1 and PPARgamma. Biochim Biophys Acta. 2004, 1636: 196-204.CrossRefPubMed Guthmann F, Schachtrup C, Tolle A, Wissel H, Binas B, Kondo H, et al: Phenotype of palmitic acid transport and of signalling in alveolar type II cells from E/H-FABP double-knockout mice: contribution of caveolin-1 and PPARgamma. Biochim Biophys Acta. 2004, 1636: 196-204.CrossRefPubMed
26.
go back to reference Lachmann RA, Werchan S, Schachtrup C, Haitsma JJ, Spener F, Lachmann B: Liver-type fatty acid binding protein in serum and broncho-alveolar lavage in a model of acute respiratory failure because of surfactant depletion – a possible marker for lung damage?. Clin Physiol Funct Imaging. 2006, 26: 371-375. 10.1111/j.1475-097X.2006.00703.x.CrossRefPubMed Lachmann RA, Werchan S, Schachtrup C, Haitsma JJ, Spener F, Lachmann B: Liver-type fatty acid binding protein in serum and broncho-alveolar lavage in a model of acute respiratory failure because of surfactant depletion – a possible marker for lung damage?. Clin Physiol Funct Imaging. 2006, 26: 371-375. 10.1111/j.1475-097X.2006.00703.x.CrossRefPubMed
27.
go back to reference Masouye I, Saurat JH, Siegenthaler G: Epidermal fatty-acid-binding protein in psoriasis, basal and squamous cell carcinomas: an immunohistological study. Dermatology. 1996, 192: 208-213.CrossRefPubMed Masouye I, Saurat JH, Siegenthaler G: Epidermal fatty-acid-binding protein in psoriasis, basal and squamous cell carcinomas: an immunohistological study. Dermatology. 1996, 192: 208-213.CrossRefPubMed
28.
go back to reference Nakamura T, Sugaya T, Kawagoe Y, Suzuki T, Inoue T, Node K: Effect of pitavastatin on urinary liver-type fatty-acid-binding protein in patients with nondiabetic mild chronic kidney disease. Am J Nephrol. 2006, 26: 82-86. 10.1159/000091956.CrossRefPubMed Nakamura T, Sugaya T, Kawagoe Y, Suzuki T, Inoue T, Node K: Effect of pitavastatin on urinary liver-type fatty-acid-binding protein in patients with nondiabetic mild chronic kidney disease. Am J Nephrol. 2006, 26: 82-86. 10.1159/000091956.CrossRefPubMed
29.
go back to reference Hofstra JM, Deegens JK, Steenbergen EJ, Wetzels JF: Urinary excretion of fatty acid-binding proteins in idiopathic membranous nephropathy. Nephrol Dial Transplant. 2008, 23: 3160-3165. 10.1093/ndt/gfn190.CrossRefPubMed Hofstra JM, Deegens JK, Steenbergen EJ, Wetzels JF: Urinary excretion of fatty acid-binding proteins in idiopathic membranous nephropathy. Nephrol Dial Transplant. 2008, 23: 3160-3165. 10.1093/ndt/gfn190.CrossRefPubMed
30.
go back to reference Morgan EA, Forootan SS, Adamson J, Foster CS, Fujii H, Igarashi M, et al: Expression of cutaneous fatty acid-binding protein (C-FABP) in prostate cancer: Potential prognostic marker and target for tumourigenicity-suppression. Int J Oncol. 2008, 32: 767-775.PubMed Morgan EA, Forootan SS, Adamson J, Foster CS, Fujii H, Igarashi M, et al: Expression of cutaneous fatty acid-binding protein (C-FABP) in prostate cancer: Potential prognostic marker and target for tumourigenicity-suppression. Int J Oncol. 2008, 32: 767-775.PubMed
31.
go back to reference Ostergaard M, Rasmussen HH, Nielsen HV, Vorum H, Orntoft TF, Wolf H, et al: Proteome profiling of bladder squamous cell carcinomas: identification of markers that define their degree of differentiation. Cancer Res. 1997, 57: 4111-4117.PubMed Ostergaard M, Rasmussen HH, Nielsen HV, Vorum H, Orntoft TF, Wolf H, et al: Proteome profiling of bladder squamous cell carcinomas: identification of markers that define their degree of differentiation. Cancer Res. 1997, 57: 4111-4117.PubMed
32.
go back to reference Teratani T, Domoto T, Kuriki K, Kageyama T, Takayama T, Ishikawa A, et al: Detection of transcript for brain-type fatty Acid-binding protein in tumor and urine of patients with renal cell carcinoma. Urology. 2007, 69: 236-240. 10.1016/j.urology.2006.09.060.CrossRefPubMed Teratani T, Domoto T, Kuriki K, Kageyama T, Takayama T, Ishikawa A, et al: Detection of transcript for brain-type fatty Acid-binding protein in tumor and urine of patients with renal cell carcinoma. Urology. 2007, 69: 236-240. 10.1016/j.urology.2006.09.060.CrossRefPubMed
33.
go back to reference Wolfrum C, Borrmann CM, Borchers T, Spener F: Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors alpha – and gamma-mediated gene expression via liver fatty acid binding protein: a signaling path to the nucleus. Proc Natl Acad Sci USA. 2001, 98: 2323-2328. 10.1073/pnas.051619898.CrossRefPubMedPubMedCentral Wolfrum C, Borrmann CM, Borchers T, Spener F: Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors alpha – and gamma-mediated gene expression via liver fatty acid binding protein: a signaling path to the nucleus. Proc Natl Acad Sci USA. 2001, 98: 2323-2328. 10.1073/pnas.051619898.CrossRefPubMedPubMedCentral
34.
go back to reference Kristiansen G, Jacob J, Buckendahl AC, Grutzmann R, Alldinger I, Sipos B, et al: Peroxisome proliferator-activated receptor gamma is highly expressed in pancreatic cancer and is associated with shorter overall survival times. Clin Cancer Res. 2006, 12: 6444-6451. 10.1158/1078-0432.CCR-06-0834.CrossRefPubMed Kristiansen G, Jacob J, Buckendahl AC, Grutzmann R, Alldinger I, Sipos B, et al: Peroxisome proliferator-activated receptor gamma is highly expressed in pancreatic cancer and is associated with shorter overall survival times. Clin Cancer Res. 2006, 12: 6444-6451. 10.1158/1078-0432.CCR-06-0834.CrossRefPubMed
Metadata
Title
Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?
Authors
Angelika Tölle
Monika Jung
Michael Lein
Manfred Johannsen
Kurt Miller
Holger Moch
Klaus Jung
Glen Kristiansen
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-248

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