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Vol. 72, No. 5, 2005
Issue release date: December 2005
Pathobiology 2005;72:233–240
(DOI:10.1159/000089417)

Expression of Liver-Type Fatty-Acid-Binding Protein, Fatty Acid Synthase and Vascular Endothelial Growth Factor in Human Lung Carcinoma

Kawamura T. · Kanno R. · Fujii H. · Suzuki T.
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Abstract

Objective: A key enzyme of fatty acid synthesis, fatty acid synthase (FAS), is expressed in human cancers, including squamous-cell carcinoma of the lung, and long-chain fatty acids are intracellularly transported and/or taken up from blood by fatty-acid-binding proteins (FABPs). Since the liver-type (L-) FABP, a member of the FABPs, is detected in a subset of gastric adenocarcinomas, the expression of FAS, L-FABP and vascular endothelial growth factor (VEGF) was investigated in human lung carcinomas to elucidate the mechanisms of production and transportation of fatty acid(s) in cancer. Methods: Expression of L-FABP, FAS and VEGF in 199 surgically resected lung carcinomas was examined immunohistochemically. Possible associations of the expression of each protein with major clinicopathological factors were analyzed. Results: L-FABP was detected in 60% (120 of 199) of the lung carcinoma cases; detection was increased in large-cell carcinoma (80%) and adenosquamous carcinoma (83%), but low in squamous-cell carcinoma (47%) and in small-cell carcinoma (57%). Overall expression of FAS was 67.3% (134 of 199 cases) and that of VEGF was 86.8% (158 of 199 cases), respectively. Expression of L-FABP was not correlated with the FAS status, but there was a tendency to co-expression of L-FABP and VEGF. There was no association between L-FABP, FAS or VEGF expression and clinicopathological data. Conclusions: L-FABP, FAS and VEGF are highly expressed in human lung cancer, and expression of L-FABP is associated with that of VEGF but not that of FAS, suggesting that L-FABP might be involved in the uptake of fatty acid(s) from the bloodstream.



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References

  1. Bass NM: The cellular fatty acid binding proteins. Aspects of structure, regulation, and function. Int Rev Cytol 1988;111:143–184.
  2. Veerkamp JH, Peeters RA, Maatman RGHJ: Structural and functional features of different types of cytoplasmic fatty acid-binding proteins. Biochim Biophys Acta 1991;1081:1–24.
  3. Veerkamp J, Maatman RGHJ, Prinsen C: Fatty acid-binding proteins: structural and functional diversity. Biochem Soc Trans 1992;20:801–805.
  4. Sacchettini JC, Gordon JI: Rat intestinal fatty acid binding protein. J Biol Chem 1993;268:18399–18402.
  5. Haunerland NH, Jacobson BL, Wesenberg G, Rayment I, Holden HM: Three-dimensional structure of the muscle fatty-acid-binding protein isolated from the desert locust Schistocerca gregaria. Biochemistry 1994;33:12378–12385.
  6. Veerkamp JH, Maatman RGHJ: Cytoplasmic fatty acid-binding proteins: Their structure and genes. Prog Lipid Res 1995;34:17–52.
  7. Bennett E, Stenvers KL, Lund PK, Popko B: Cloning and characterization of a cDNA encoding a novel fatty acid binding protein from rat brain. J Neurochem 1994;63:1616–1624.
  8. Oko R, Morales CR: A novel testicular protein, with sequence similarities to a family of lipid binding proteins, is a major component of the rat sperm perinuclear theca. Dev Biol 1994;166:235–245.
  9. Chan L, Wei CF, Li WH, Yang CY, Ratner P, Pownall H, Gotto AM Jr, Smith LC: Human liver fatty acid binding protein cDNA and amino acid sequence: functional and evolutionary implications. J Biol Chem 1985;260:2629–2632.
  10. Suzuki T, Ono T: Immunohistochemical studies on the distribution and frequency of fatty-acid-binding protein positive cells in human fetal, newborn and adult liver tissues. J Pathol 1987;153:385–394.
  11. Suzuki T, Hitomi M, Ono T: Immunohistochemical distribution of hepatic fatty acid-binding protein in rat and human alimentary tract. J Histochem Cytochem 1988;36:349–357.
  12. Suzuki T, Ono T: Ontogeny of hepatic fatty acid-binding protein immunoreactivity in human liver and intestinal tract. Acta Pathol Jpn 1998;38:979–987.

    External Resources

  13. Suzuki T, Watanabe K, Ono T: Immunohistochemical demonstration of liver fatty acid-binding protein in human hepatocellular malignancies. J Pathol 1990;161:79–83.
  14. Suzuki T, Watanabe K, Hirota M, Iwafuchi M, Ono T, Aoyagi Y, Ito S: Establishment of a human hepatoblastoma model in a thymic nude mice: producibility of fatty acid-binding protein, α-fetoprotein and α-acid glycoprotein. Acta Pathol Jpn 1992;42:255–261.
  15. Hashimoto T, Kusakabe K, Watanabe K, Sugino T, Fukuda T, Nashimoto A, Honma K, Sato Y, Kimura H, Fujii H, Suzuki T: Liver-type fatty acid-binding protein is highly expressed in intestinal metaplasia and in subset of carcinomas of the stomach without association with fatty acid synthase status in the carcinoma. Pathobiology 2004;71:115–122.
  16. Sacchetti JC, Scapin G, Gopaul D, Gordon JI: Refinement of the structure of Escherichia coli-derived rat intestinal fatty acid binding protein with bound oleate to 1.75-A resolution: correlation with the structures of apoprotein and the protein with bound palmitate. J Biol Chem 1992;267:23534–23545.

    External Resources

  17. Richieri GV, Ogata RT, Kleinfield AM: Equilibrium constants for the binding of fatty acids with fatty acid-binding proteins from adipocyte, intestine, heart and liver measured with the fluorescent probe ADIFAB. J Biol Chem 1994;269:23918–23930.
  18. Burrier RE, Manson CE, Brecher P: Binding of acyl-CoA to liver fatty acid binding protein: effect on acyl-CoA synthesis. Biochim Biophys Acta 1987;919:221–230.
  19. Takikawa H, Kaplowitz N: Binding of bile acids, oleic acid, and organic anions by rat and human hepatic Z protein. Arch Biochem Biophys 1986;251:385–392.
  20. Thumser AE, Voysey JE, Wilton DC: The binding of lysophospholipids to rat liver fatty acid-binding protein and albumin. Biochem J 1994;301:801–806.
  21. Burrier RE, Brecher P: Binding of lysophosphatidylcholine to the rat liver fatty acid binding protein. Biochim Biophys Acta 1986;879:229–239.
  22. Richieri GV, Ogata RT, Kleinfeld AM: Fatty acid interactions with native and mutant fatty acid binding proteins. Mol Cell Biochem 1999;192:77–85.
  23. Richieri GV, Ogata RT, Kleinfeld AM: Thermodynamic and kinetic properties of fatty acid interactions with rat liver fatty acid-binding protein. J Biol Chem 1996;271:31068–31074.
  24. Bressler R, Wakil SJ: Studies on the mechanism of fatty acid synthesis: the conversion of malonyl coenzyme A to long chain fatty acid. J Biol Chem 1961;236:1643–1651.
  25. Wakil SJ: Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry 1989;28:4523–4530.
  26. Kuhajda FP, Jenner K, Wood FD, Hennigar RA, Jacobs LB, Dick JD, Pasternack GR: Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc Natl Acad Sci USA 1994;91:6379–6383.
  27. Takahashi K, Odani S, Ono T: Isolation and characterization of three fractions (DE-I, DE-II, and DE-III) of rat liver Z-protein and the complete primary structure of DE-II. Eur J Biochem 1983;136:589–601.
  28. Piyathilake CJ, Frost AR, Manne U, Bell WC, Weiss H, Heimberger DG, Grizzle WE: The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung. Hum Pathol 2000;31:1068–1073.
  29. Epstein JI, Carmichael M, Partin AW: OA-519 (fatty acid synthase) as an independent predictor of pathologic stage in adenocarcinoma of the prostate. Urology 1995;45:81–86.
  30. Gransler TS, Hardman W, Hunt DA, Schaffel S, Hennigar RA: Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival. Hum Pathol 1997;28:686–692.
  31. Jensen V, Ladekarl M, Holm-Nielsen P, Melsen F, Soerensen FB: The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB 1 in node-negative breast cancer. J Pathol 1995;176:343–352.
  32. Nakamura I, Kimijima I, Zhang GJ, Onogi H, Endo I, Suzuki S, Tsuchiya A, Takenoshita S, Kusakabe T, Suzuki T: Fatty acid synthase expression in Japanese breast carcinoma patients. Int J Mol Med 1999;4:381–387.
  33. Rashid A, Pizer ES, Moga M, Hamilton SR: Elevation of fatty acid synthase expression and fatty acid synthetic activity in colorectal neoplasia. Am J Pathol 1997;150:201–208.
  34. Nemoto T, Terashima S, Kogure M, Hoshino Y, Kusakabe T, Suzuki T, Gotoh M: Overexpression of fatty acid synthase in oesophageal squamous cell dysplasia and carcinoma. Pathobiology 2001;69:297–303.
  35. Kusakabe T, Nashimoto A, Honma K, Suzuki T: Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach. Histopathology 2002;40:71–79.
  36. Hayashi T, Abe K, Suzuki H, Itoyama Y: Rapid induction of vascular endothelial growth factor gene expression after transient middle cerebral artery occlusion in rats. Stroke 1997;28:2039–2044.
  37. Torimura T, Sata M, Ueno T, Kin M, Tsuji R, Suzaku K, Hashimoto O, Sugawara H, Tanikawa K: Increased expression of vascular endothelial growth factor is associated with tumor progression in hepatocellular carcinoma. Hum Pathol 1998;29:986–991.
  38. Yuan A, Yu CJ, Chen WJ, Lin FY, Kuo SH, Luh KT, Yang PC: Correlation of total VEGF mRNA and protein expression with histologic type, tumor angiogenesis, patient survival and timing of relapse in non-small cell lung cancer. Int J Cancer 2000;89:475–483.
  39. Storch J, Thumser AE: The fatty acid transport function of fatty acid-binding proteins. Biochim Biophys Acta 2000;1486:28–44.
  40. Murphy EJ, Prows DR, Jefferson JR, Schroeder F: Liver fatty acid-binding protein expression in transfected fibroblasts stimulates fatty acid uptake and metabolism. Biochim Biophys Acta 1996;1301:191–198.

    External Resources

  41. Wolfrum C, Buhlmann C, Rolf B, Borchers T, Spener F: Variation of liver-type fatty acid binding protein content in the human hepatoma cell line HepG2 by peroxisome proliferators and antisense RNA affects the rate of fatty acid uptake. Biochim Biophys Acta 1999;1437:28–44.


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