Medical Oncology

, Volume 21, Issue 3, pp 241–250 | Cite as

Serum semicarbazide-sensitive amine oxidase (SSAO) activity correlates with VEGF in non-small-cell lung cancer patients

  • Håkan Garpenstrand
  • Michael Bergqvist
  • Daniel Brattström
  • Anders Larsson
  • Lars Oreland
  • Patrik Hesselius
  • Gunnar Wagenius
Original Article


Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme associated with vascular systems in mammals. SSAO catalyzes the deamination of primary monoamines and has been suggested to be a risk factor in vascular disorders, e.g., diabetic vascular complications. The primary aim of the present study was to investigate if serum SSAO activity is associated with clinical parameters in non-small cell lung cancer (NSCLC) patients. Secondary aims were to investigate if there is a correlation between SSAO activity and the angiogenic factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).

Thirty-three patients donated 231 serum samples. Detectable levels of bFGF, VEGF, and SSAO were observed in all patients. Serum SSAO activity was not statistically associated with survival (p=0.35). A highly significant statistical correlation was found between SSAO activity and VEGF (p<0.0001). No significant correlation between SSAO and bFGF was observed.

We conclude that SSAO was not associated with survival in patients with NSCLC. However, a strong correlation between serum SSAO activity and the angiogenic factor VEGF was found that might implicate new aspects of the mechanisms controlling angiogenesis.

Key Words

Non-small cell lung cancer SSAO vascular endothelial growth factor (VEGF) basic fibroblast growth factor (bFGF) angiogenesis 


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  1. 1.
    Lyles GA. Mammalian plasma and tissue-bound semicarbazide-sensitive amine oxidases: biochemical, pharmacological and toxicological aspects. Int J Biochem Cell Biol 1996; 28: 259–274.PubMedCrossRefGoogle Scholar
  2. 2.
    Lewinsohn R. Mammalian monoamine-oxidizing enzymes, with special reference to benzylamine oxidase in human tissues. Braz J Med Biol Res 1984; 17: 223–256.PubMedGoogle Scholar
  3. 3.
    Mercier N, Moldes M, El Hadri K, Feve B. Regulation of semicarbazide-sensitive amine oxidase expression by tumor necrosis factor-alpha in adipocytes: functional consequences on glucose transport. J Pharmacol Exp Ther 2003; 304: 1197–1208.PubMedCrossRefGoogle Scholar
  4. 4.
    Enrique-Tarancon G, et al. Role of semicarbazide-sensitive amine oxidase on glucose transport and GLUT4 recruitment to the cell surface in adipose cells. J Biol Chem 1998; 273: 8025–8032.PubMedCrossRefGoogle Scholar
  5. 5.
    Smith DJ, Salmi M, Bono P, Hellman J, Leu T, Jalkanen S. Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion molecule. J Exp Med 1998; 188: 17–27.PubMedCrossRefGoogle Scholar
  6. 6.
    Boomsma F, et al. Plasma semicarbazide-sensitive amine oxidase is elevated in patients with congestive heart failure. Cardiovasc Res 1997; 33: 387–391.PubMedCrossRefGoogle Scholar
  7. 7.
    McEwen CM, Jr Harrison, DC. Abnormalities of serum monoamine oxidase in chronic congestive heart failure. J Lab Clin Med 1965; 65: 546–559.PubMedGoogle Scholar
  8. 8.
    Boomsma F, Derkx FH, van den Meiracker AH, Man in’t Veld AJ, Schalekamp MA. Plasma semicarbazide-sensitive amine oxidase activity is elevated in diabetes mellitus and correlates with glycosylated haemoglobin. Clin Sci (Lond) 1995; 88: 675–679.Google Scholar
  9. 9.
    Garpenstrand H, Ekblom J, Backlund LB, Oreland L, Rosenqvist U. Elevated plasma semicarbazide-sensitive amine oxidase (SSAO) activity in type 2 diabetes mellitus complicated by retinopathy. Diabet Med 1999; 16: 514–521.PubMedCrossRefGoogle Scholar
  10. 10.
    McEwen CM, Jr, Castell DO. Abnormalities of serum monoamine oxidase in chronic liver disease. J Lab Clin Med 1967; 70: 36–47.PubMedGoogle Scholar
  11. 11.
    Sikkema JM, Franx A, Fijnheer R, Nikkels PG, Bruinse HW, Boomsma F. Semicarbazide-sensitive amine oxidase in pre-eclampsia: no relation with markers of endothelial cell activation. Clin Chim Acta 2002; 324: 31–38.PubMedCrossRefGoogle Scholar
  12. 12.
    Lewinsohn R. Human serum amine oxidase. Enzyme activity in severely burnt patients and in patients with cancer. Clin Chim Acta 1977; 81: 247–256.PubMedCrossRefGoogle Scholar
  13. 13.
    Ekblom J, Gronvall J, Lennernast B, Nilsson S, Garpenstrand H, Oreland L. Elevated activity of semicarbazide-sensitive amine oxidase in blood from patients with skeletal metastases of prostate cancer. Clin Sci (Lond) 1999; 97: 111–115.CrossRefGoogle Scholar
  14. 14.
    Lizcano JM, Escrich E, Ribalta T, Muntane J, Unzeta M. Amine oxidase activities in rat breast cancer induced experimentally with 7,12-dimethylbenz(alpha)anthracene. Biochem Pharmacol 1991; 42: 263–269.PubMedCrossRefGoogle Scholar
  15. 15.
    Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182–1186.PubMedCrossRefGoogle Scholar
  16. 16.
    Jussila L, Alitalo K. Vascular growth factors and lymphangiogenesis. Physiol Rev 2002; 82: 673–700.PubMedGoogle Scholar
  17. 17.
    Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990; 82: 4–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Drevs J, Laus C, Mendinger M, Schmidt-Gersbach C, Unger C. Antiangiogenesis: current clinical data and future perspectives. Onkologie 2002; 25: 520–527.PubMedCrossRefGoogle Scholar
  19. 19.
    Bates DO, Hillman NJ, Williams B, Neal CR, Pocock TM. Regulation of microvascular permeability by vascular endothelial growth factors. J Anat 2002; 200: 581–597.PubMedCrossRefGoogle Scholar
  20. 20.
    Karayiannakis AJ, et al. Clinical significance of preoperative serum vascular endothelial growth factor levels in patients with colorectal cancer and the effect of tumor surgery. Surgery 2002; 131: 548–555.PubMedCrossRefGoogle Scholar
  21. 21.
    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.PubMedGoogle Scholar
  22. 22.
    Jacobsen J, Rasmuson T, Grankvist K, Ljungberg B. Vascular endothelial growth factor as prognostic factor in renal cell carcinoma. J Urol 2000; 163: 343–347.PubMedCrossRefGoogle Scholar
  23. 23.
    Bates DO, Harper SJ. Regulation of vascular permeability by vascular endothelial growth factors. Vascul Pharmacol 2002; 39: 225–237.PubMedCrossRefGoogle Scholar
  24. 24.
    Powers CJ, McLeskey SW, Wellstein A. Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer 2000; 7: 165–197.PubMedCrossRefGoogle Scholar
  25. 25.
    Mountain CF, Greenberg SD, Fraire AE. Tumor stage in non-small cell carcinoma of the lung. Chest 1991; 99: 1258–1260.PubMedGoogle Scholar
  26. 26.
    Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin 1999; 49: 33–64, 1.PubMedGoogle Scholar
  27. 27.
    Sarabia SF, Liehr JG. Induction of monoamine oxidase B by 17 beta-estradiol in the hamster kidney preceding carcinogenesis. Arch Biochem Biophys 1998; 355: 249–253.PubMedCrossRefGoogle Scholar
  28. 28.
    ThyagaRajan S, Felten SY, Felten DL. Antitumor effect of L-deprenyl in rats with carcinogen-induced mammary tumors. Cancer Lett 1998; 123: 177–183.PubMedCrossRefGoogle Scholar
  29. 29.
    Ekblom J. Potential therapeutic value of drugs inhibiting semicarbazide-sensitive amine oxidase: vascular cytoprotection in diabetes mellitus. Pharmacol Res 1998; 37: 87–92.PubMedCrossRefGoogle Scholar
  30. 30.
    Langford SD, Trent MB, Balakumaran A, Boor PJ. Developmental vasculotoxicity associated with inhibition of semicarbazide-sensitive amine oxidase. Toxicol Appl Pharmacol 1999; 155: 237–244.PubMedCrossRefGoogle Scholar
  31. 31.
    Brattstrom D, et al. Elevated preoperative serum levels of angiogenic cytokines correlate to larger primary tumours and poorer survival in non-small cell lung cancer patients. Lung Cancer 2002; 37: 57–63.PubMedCrossRefGoogle Scholar
  32. 32.
    Brattstrom D, Bergqvist M, Hesselius P, Larsson A, Wagenius G, Brodin O. Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer. Lung Cancer 2004; 43: 55–62.PubMedCrossRefGoogle Scholar
  33. 33.
    Jelkmann W. Pitfalls in the measurement of circulating vascular endothelial growth factor. Clin Chem 2001; 47: 617–623.PubMedGoogle Scholar
  34. 34.
    Banks RE, et al. Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology. Br J Cancer 1998; 77: 956–964.PubMedGoogle Scholar
  35. 35.
    Tamura M, et al. Plasma VEGF concentration can predict the tumor angiogenic capacity in non-small cell lung cancer. Oncol Rep 2001; 8: 1097–1102.PubMedGoogle Scholar
  36. 36.
    Choi JH, et al. Vascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts. Lung Cancer 2001; 33: 171–179.PubMedCrossRefGoogle Scholar
  37. 37.
    Brattstrom D, et al. Basic fibroblast growth factor and vascular endothelial growth factor in sera from non-small cell lung cancer patients. Anticancer Res 1998; 18: 1123–1127.PubMedGoogle Scholar
  38. 38.
    Matsuyama W, et al. Serum levels of vascular endothelial growth factor dependent on the stage progression of lung cancer. Chest 2000; 118: 948–951.PubMedCrossRefGoogle Scholar
  39. 39.
    Laack E, et al. Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer. Ann Oncol 2002; 13: 1550–1557.PubMedCrossRefGoogle Scholar
  40. 40.
    Maniwa Y, Okada M, Ishii N, Kiyooka K. Vascular endothelial growth factor increased by pulmonary surgery accelerates the growth of micrometastases in metastatic lung cancer. Chest 1998; 114: 1668–1675.PubMedGoogle Scholar
  41. 41.
    Kido Y. Vascular endothelial growth factor (VEGF) serum concentration changes during chemotherapy in patients with lung cancer. Kurume Med J 2001; 48: 43–47.PubMedGoogle Scholar
  42. 42.
    Takigawa N, Segawa Y, Fujimoto N, Hotta K, Eguchi K. Elevated vascular endothelial growth factor levels in sera of patients with lung cancer. Anticancer Res 1998; 18: 1251–1254.PubMedGoogle Scholar
  43. 43.
    Roselli M, et al. Vascular endothelial growth factor (VEGF-A) plasma levels in non-small cell lung cancer: relationship with coagulation and platelet activation markers. Thromb Haemost 2003; 89: 177–184.PubMedGoogle Scholar
  44. 44.
    Tamura M, Ohta Y, Nakamura H, Oda M, Watanabe G. Diagnostic value of plasma vascular endothelial growth factor as a tumor marker in patients with non-small cell lung cancer. Int J Biol Markers 2002; 17: 275–279.PubMedGoogle Scholar
  45. 45.
    Kishiro I, Kato S, Fuse D, Yoshida T, Machida S, Kaneko N. Clinical significance of vascular endothelial growth factor in patients with primary lung cancer. Respirology 2002; 7: 93–98.PubMedCrossRefGoogle Scholar
  46. 46.
    Lee JK, Hong YJ, Han CJ, Hwang DY, Hong SI. Clinical usefulness of serum and plasma vascular endothelial growth factor in cancer patients: which is the optimal specimen? Int J Oncol 2000; 17: 149–152.PubMedGoogle Scholar
  47. 47.
    Salgado R, et al. Platelet number and interleukin-6 correlate with VEGF but not with bFGF serum levels of advanced cancer patients. Br J Cancer 1999; 80: 892–897.PubMedCrossRefGoogle Scholar
  48. 48.
    Salgado R, Vermeulen PB, Van Marck E, Benoy I, Dirix L. Correspondence re: M. L. George et al., Correlation of plasma and serum vascular endothelial growth factor levels with platelet count in colorectal cancer: clinical evidence of platelet scavenging? Clin. Cancer Res., 6: 3147–3152, 2000. Clin Cancer Res 2001; 7: 1481–1483.Google Scholar

Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Håkan Garpenstrand
    • 2
  • Michael Bergqvist
    • 1
  • Daniel Brattström
    • 1
  • Anders Larsson
    • 3
  • Lars Oreland
    • 2
  • Patrik Hesselius
    • 1
  • Gunnar Wagenius
    • 1
  1. 1.Department of Oncology, Radiology, Clinical Immunology, Section of OncologyUppsala University HospitalUppsalaSweden
  2. 2.Department of Neuroscience, Unit of PharmacologyUppsala UniversityUppsalaSweden
  3. 3.Department of Medical Sciences, Clinical ChemistryUniversity HospitalUppsalaSweden

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