Journal of the Korean Association of Oral and Maxillofacial Surgeons

  • 제32권1호
  • /
  • Pages.8-18
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  • 2006
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  • 2234-7550(pISSN)
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  • 2234-5930(eISSN)
대한구강악안면외과학회 (The Korean Association of Oral and Maxillofacial Surgeons)
권호 표지

Expression of angiogenin, TGF-${\beta}$, VEGF, APEX and TNF-${\alpha}$ in oral squamous cell carcinoma

  • Lee, Ho-Sun (Department of Oral & Maxillofacial Surgery, College of Medicine, and Medical Research Institute, Chungbuk National University) ;
  • Kim, Kyoung-Won (Department of Oral & Maxillofacial Surgery, College of Medicine, and Medical Research Institute, Chungbuk National University) ;
  • Kim, Wun-Jae (Department of Urology, College of Medicine, and Medical Research Institute, Chungbuk National University)
  • 발행 : 2006.02.28
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초록

Purpose: The purpose of this study was to verify that the expressions of angiogenin, transforming growth factor-beta(TGF-${\beta}$), vascular endothelial growth factor(VEGF), human apurinic/apyrimidinic endonuclease(APEX) and tumor necrosis factor-alpha(TNF-${\alpha}$) were associated with the tumorigenesis of the oral squamous cell carcinoma(OSCC). Materials and Methods: Fifty-one samples of OSCC and fifteen normal oral mucosae were obtained to analyze the expression levels of above five factors. mRNA expressions were quantified by the quantitative competitive PCR(QC-PCR) method. After 2% agarose gel electrophoresis stained with ethidium bromide, the concentration of mRNA was calculated by a digital image analysis system. The expression levels of angiogenin, TGF-${\beta}$, VEGF, APEX and TNF-${\alpha}$ were compared by unpaired Student's t-tests between cancer and normal tissues. We analyzed statistically to find the cut-off values that would be useful as diagnostic markers, and the linear regression analysis between every two factors of these five factors by SAS system. Results: All of these five factors (angiogenin: P<0.0037, TGF-${\beta}$: P<0.0001, VEGF: P<0.0102, APEX: P<0.0023, TNF-${\alpha}$: P<0.0074) were significantly correlated with OSCC. In the analysis to find the cut-off values for the diagnosis, we could not find any value that had a reasonable sensitivity and specificity. In the linear regression analysis, there were correlations between angiogenin and TNF-${\alpha}$, TGF-${\beta}$ and VEGF, TGF-${\beta}$ and APEX, TGF-${\beta}$ and TNF-${\alpha}$, VEGF and APEX, VEGF and TNF-${\alpha}$, APEX and TNF-${\alpha}$. Conclusion: Our results suggest that not only angiogenin, TGF-${\beta}$, VEGF, APEX and TNF-${\alpha}$ are significantly associated with the tumorigenesis, but also the close relationship between these factors might enhance the tumorigenesis of OSCC. We can not find clinical availability for diagnosis.

키워드

참고문헌

  1. Bussolino F, Mantovani A, Persico G: Molecular mechanisms of blood vessel formation. Trends Biochem Sci 1997;22:251-256 https://doi.org/10.1016/S0968-0004(97)01074-8
  2. Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86:353-364 https://doi.org/10.1016/S0092-8674(00)80108-7
  3. Shapiro R, Strydom DJ, Olson KA, Vallee BL: Isolation of angiogenin from normal human plasma. Biochemistry 1987;26:5141-5146 https://doi.org/10.1021/bi00390a037
  4. Rybak SM, Fett JW, Yao Q-Z, Vallee BL: Angiogenin mRNA in human tumor and normal cells. Biochem. Biophys Res Commun 1987;146:1240-1248 https://doi.org/10.1016/0006-291X(87)90781-9
  5. Olson KA, Fett JW, French TC, Key ME, Vallee BL: Angiogenin Antagonists Prevent Tumor Growth in vivo. Proc Natl Acad Sci USA 1995;92:442-446
  6. Olson KA, Byers HR, Key ME, Fett JW: Inhibition of prostate carcinoma establishment and metastatic growth in mice by an antiangiogenin monoclonal antibody. Int J Cancer 2002;98:923-929 https://doi.org/10.1002/ijc.10282
  7. Etoh T, Shibuta K, Barnard GF, Kitano S, Mori M: Angiogenin expression in human colorectal cancer: the role of focal macrophage infiltration. Clin Cancer Res 2000; 6:3545-551
  8. Eberle K, Oberpichler A, Trantakis C, Krupp W, Knupfer M, Tschesche H, Seifert V: The expression of angiogenin in tissue samples of different brain tumours and cultured glioma cells. Anticancer Res 2000;20:1679-1684
  9. Shimoyama S, Kaminishi M: Increased angiogenin expression in gastric cancer correlated with cancer progression. J Cancer Res Clin Oncol 2000;126:468-474 https://doi.org/10.1007/s004320000138
  10. Wechsel HW, Bichler KH, Feil G, Loeser W, Lahme S, Petri E: Renal cell carcinoma: relevance of angiogenetic factors. Anticancer Res 1999;19:1537-1540
  11. Ugurel S, Rappl G, Tilgen W, Reinhold U: Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival. J Clin Oncol 2001;19:577-583 https://doi.org/10.1200/JCO.2001.19.2.577
  12. Connolly DT: Vascular permeability factor: a unique regulator of blood vessel function. J Cell Biochem 1991;47:219- 223 https://doi.org/10.1002/jcb.240470306
  13. Ferrara N, Houck KL. Jakeman L, Leung DW: Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 1992;13:18-32 https://doi.org/10.1210/edrv-13-1-18
  14. Otani N, Minami S, Yamoto M: The vascular endothelial growth factor/fms-like tyrosine kinase system in human ovary during the menstrual cycle and early pregnancy. J Clin Endocrinol Metab 1999;84:3845-3851 https://doi.org/10.1210/jc.84.10.3845
  15. Roberts WG, Palade GE: Neovasculature induced by vascular endothelial growth factor is fenestrated. Cancer Res 1997;57:765-772
  16. Takano S, Yoshii Y, Kondo S, Suzuki H, Maruno T, Shirai S, Nose T: Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients. Cancer Res 1996;56:2185-2190
  17. Salven P, Manpaa H, Orpana A, Alitalo K, Joensuu H: Serum vascular endothelial growth factor is often elevated in disseminated cancer. Clin Cancer Res 1997;3:647-651
  18. Lindhal T: Suppression of spontaneous mutagenesis in human cells by DNA base excision-repair. Mutat Res 2000;462:129-135 https://doi.org/10.1016/S1383-5742(00)00024-7
  19. Wilson DMIII, Barsky D: The major human abasic endonuclease: formation, consequences and repair of abasic lesions in DNA. Mutat Res 2001;485:283-307 https://doi.org/10.1016/S0921-8777(01)00063-5
  20. Xanthoudakis S, Smeyne RJ, Wallace JD, Curran T: The redox/ DNA repair protein, Ref-1, is essential for early embryonic development in mice. Proc Natl Acad Sci USA 1996;93:8919-8923
  21. Bobola MS, Blank A, Berger MS, Stevens BA, Silber JR: Apurinic/apyrimidinic endonuclease activity is elevated in human adult gliomas. Clin Cancer Res 2001;7:3510-3518
  22. Silber JR, Bobola MS, Blank A, Schoeler KD, Haroldson PD, Huynh MB: Kolstoe The Apurinic/Apyrimidinic Endonuclease Activity of Ape1/Ref-1 Contributes to Human Glioma Cell Resistance to Alkylating Agents and is Elevated by Oxidative Stress. Clin Cancer Res 2002;8:3008- 3018
  23. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Willaiamson B: An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 1975;25:3666-3670
  24. Sasaki M, Nakajima K, Perinchery G, Fujino T, Oh BR, Fujimoto S, et al.: Frequent genotype changes at -308 of the human tumor necrosis factor-alpha promoter region in human uterine endometrial cancer. Oncol Rep 2000;7:369-373
  25. Derynck R, Akhurst RJ, Balmain A: TGF-$\beta$ signaling in tumor suppression and cancer progression. Nat Genet 2001;29:117-129 https://doi.org/10.1038/ng1001-117
  26. Wakefield LM, Roberts AB: TGF-beta signaling: positive and negative effects on tumorigenesis. Curr Opin Genet Dev 2002;12:22-29 https://doi.org/10.1016/S0959-437X(01)00259-3
  27. Cui W, Fowlis DJ, Bryson S: TGF-beta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 1996;86:531-542 https://doi.org/10.1016/S0092-8674(00)80127-0
  28. Gorsch SM, Memoli VA, Stukel TA, Gold LI, Arrick BA: Immunohistochemical staining for transforming growth factor beta 1 associates with disease progression in human breast cancer. Cancer Res 1992;52:6949-6952
  29. Reed JA, McNutt NS, Prieto VG, Albino AP: Expression of transforming growth factor-beta 2 in malignant melanoma correlates with the depth of tumor invasion. Implications for tumor progression. Am J Pathol 1994;145:97-104
  30. Dumont N: Genetic and epigenetic contributions to colorectal cancer. APMIS 1999;107:711-722 https://doi.org/10.1111/j.1699-0463.1999.tb01466.x
  31. Oft M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E: TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev 1996;10:2462-2477 https://doi.org/10.1101/gad.10.19.2462
  32. Folkman J: Anti-angiogenesis: new concept for therapy of solid tumors. Ann Surg 1972;175:409-416 https://doi.org/10.1097/00000658-197203000-00014
  33. Rafii S: Circulating endothelial precursors: mystery, reality, and promise. J Clin Invest 2000;105:17-19 https://doi.org/10.1172/JCI8774
  34. Montero S, Guzman C, Cortes FH, Colomer R: Angiogenin expression and prognosis in primary breast carcinoma. Clin Cancer Res 1998;4:2161-2168
  35. Baek JH, Jang JE, Kang CM, Chung HY, Kim ND, Kim KW: Hypoxia-induced VEGF enhances tumor survivability via suppression of serum deprivation-induced apoptosis. Oncogene 2000;19:4621-46318 https://doi.org/10.1038/sj.onc.1203814
  36. Wong YK, Liu CJ, Kwan PC, Chao SY: Microvascular density and vascular endothelial growth factor immunoreactivity as predictors of regional lymph node metastasis from betel-associated oral squamous cell carcinoma. J Oral Maxillofac Surg 2003;61:1257-1262 https://doi.org/10.1016/S0278-2391(03)00725-0
  37. Kishimoto K, Sasaki A, Yoshihama Y, Mese H, Tsukamoto G, Matsumura T: Expression of vascular endothelial growth factor-C predicts regional lymph node metastasis in early oral squamous cell carcinoma. Oral Oncol 2003;39:391-396 https://doi.org/10.1016/S1368-8375(02)00143-4
  38. Okamoto M, Nishimine M, Kishi M, Kirita T, Sugimura M, Nakamura M, Konishi N: Prediction of delayed neck metastasis in patients with stage I/II squamous cell carcinoma of the tongue. J Oral Pathol Med 2002;31:227-233 https://doi.org/10.1034/j.1600-0714.2002.310406.x
  39. Cuturi MC, Murphy M, Costa-Giomi MP, Weinmann R, Perussia B, Trinchieri G: Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med 1987;165:1581-1594 https://doi.org/10.1084/jem.165.6.1581
  40. Frater-Schroder M, Risau W, Hallmann R, Gautschi P, Bohlen P: Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc Natl Acad Sci USA 1987;84:5277-5281
  41. Nakano Y, Kobayashi W, Sugai S, Kimura H, Yagihashi S: Expression of tumor necrosis factor-alpha and interleukin-6 in oral squamous cell carcinoma. Jpn J Cancer Res 1999;90:858-866 https://doi.org/10.1111/j.1349-7006.1999.tb00827.x
  42. Kurokawa H, Yamashita M, Yamashita Y, Murata T, Miura K, Kajiyama M: Estimation of tumor necrosis factor-alpha in the diagnosis, the prognosis and the treatment follow-up of oral squamous cell carcinoma. Fukuoka Igaku Zasshi 1998;89:312-320