Skip to main content

Advertisement

SpringerLink
Log in

Increase of angiogenic growth factors after hepatic artery embolization in patients with neuroendocrine tumours

  • Research Article
  • Published:
Tumor Biology

Abstract

In the event of diffuse hepatic metastases, hepatic artery embolization (HAE) can be a successful treatment option in patients with well-differentiated neuroendocrine tumours (NET). However, embolization causes hypoxia which stimulates angiogenesis and therefore tumour growth. This study investigates angiogenesis activity following HAE by measuring vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and C-terminal proendothelin-1 (proET-1) in blood. Twelve patients with well-differentiated NET and liver metastases underwent HAE. VEGF, ET-1 and proET-1 were measured before embolization and the days following treatment during hospitalization. Mean levels during treatment were compared with those at baseline. From 12 patients, 90 blood samples were obtained before and daily for 8 days following HAE. Mean (±SE) VEGF level at baseline was 116 (±33) ng/l which increased after HAE to 313 (±46) ng/l at day 6, followed by a gradual decrease. ProET-1 showed a similar pattern, with a mean baseline level of 9.2 (±2.0) pmol/l and the highest level of 40.8 (±5.7) pmol/l at day 6. Some fluctuations were observed for ET-1, with maximum levels at day 3 compared to baseline levels. In patients with well-differentiated NET who underwent hepatic arterial embolization, angiogenic growth factors increase temporarily. This implies a need to investigate the effect of anti-angiogenic drugs as an adjuvant therapy to embolization.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Taal BG, Visser O. Epidemiology of neuroendocrine tumours. Neuroendocrinology. 2004;80 Suppl 1:3–7.

    Article  PubMed  CAS  Google Scholar 

  2. Zuetenhorst JM, Taal BG. Metastatic carcinoid tumors: a clinical review. Oncologist. 2005;10(2):123–31.

    Article  PubMed  Google Scholar 

  3. O'Toole D, Maire F, Ruszniewski P. Ablative therapies for liver metastases of digestive endocrine tumours. Endocr-Relat Cancer. 2003;10(4):463–8.

    Article  PubMed  Google Scholar 

  4. Que FG, Nagorney DM, Batts KP, Linz LJ, Kvols LK. Hepatic resection for metastatic neuroendocrine carcinomas. Am J Surg. 1995;169(1):36–42.

    Article  PubMed  CAS  Google Scholar 

  5. Kvols LK, Moertel CG, O'Connell MJ, Schutt AJ, Rubin J, Hahn RG. Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue. N Engl J Med. 1986;315(11):663–6.

    Article  PubMed  CAS  Google Scholar 

  6. Wymenga AN, Eriksson B, Salmela PI, Jacobsen MB, Van Cutsem EJ, Fiasse RH, et al. Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms. J Clin Oncol. 1999;17(4):1111.

    PubMed  CAS  Google Scholar 

  7. Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999;340(11):858–68.

    Article  PubMed  CAS  Google Scholar 

  8. Saltz L, Trochanowski B, Buckley M, Heffernan B, Niedzwiecki D, Tao Y, et al. Octreotide as an antineoplastic agent in the treatment of functional and nonfunctional neuroendocrine tumors. Cancer. 1993;72(1):244–8.

    Article  PubMed  CAS  Google Scholar 

  9. Eriksson BK, Larsson EG, Skogseid BM, Lofberg AM, Lorelius LE, Oberg KE. Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors. Cancer. 1998;83(11):2293–301.

    Article  PubMed  CAS  Google Scholar 

  10. Gupta S, Johnson MM, Murthy R, Ahrar K, Wallace MJ, Madoff DC, et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer. 2005;104(8):1590–602.

    Article  PubMed  Google Scholar 

  11. Strosberg JR, Choi J, Cantor AB, Kvols LK. Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Control. 2006;13(1):72–8.

    PubMed  Google Scholar 

  12. Roche A, Girish BV, de Baere T, Ducreux M, Elias D, Laplanche A, et al. Prognostic factors for chemoembolization in liver metastasis from endocrine tumors. Hepatogastroenterology. 2004;51(60):1751–6.

    PubMed  CAS  Google Scholar 

  13. Ruszniewski P, Malka D. Hepatic arterial chemoembolization in the management of advanced digestive endocrine tumors. Digestion. 2000;62 Suppl 1:79–83.

    Article  PubMed  Google Scholar 

  14. Meij V, Zuetenhorst JM, van Hillegersberg R, Kroger R, Prevoo W, van Coevorden F, et al. Local treatment in unresectable hepatic metastases of carcinoid tumors: experiences with hepatic artery embolization and radiofrequency ablation. World J Surg Oncol. 2005;3:75.

    Article  PubMed  Google Scholar 

  15. Kim KW, Bae SK, Lee OH, Bae MH, Lee MJ, Park BC. Insulin-like growth factor II induced by hypoxia may contribute to angiogenesis of human hepatocellular carcinoma. Cancer Res. 1998;58(2):348–51.

    PubMed  CAS  Google Scholar 

  16. Wu XZ, Xie GR, Chen D. Hypoxia and hepatocellular carcinoma: the therapeutic target for hepatocellular carcinoma. J Gastroenterol Hepatol. 2007;22(8):1178–82.

    Article  PubMed  CAS  Google Scholar 

  17. Sun HC, Tang ZY. Angiogenesis in hepatocellular carcinoma: the retrospectives and perspectives. J Cancer Res Clin Oncol. 2004;130(6):307–19.

    Article  PubMed  Google Scholar 

  18. Poon RT, Lau C, Yu WC, Fan ST, Wong J. High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: a prospective study. Oncol Rep. 2004;11(5):1077–84.

    PubMed  CAS  Google Scholar 

  19. Khan SQ, Dhillon O, Struck J, Quinn P, Morgenthaler NG, Squire IB, et al. C-terminal pro-endothelin-1 offers additional prognostic information in patients after acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) Study. Am Heart J. 2007;154(4):736–42.

    Article  PubMed  CAS  Google Scholar 

  20. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.

    Article  PubMed  CAS  Google Scholar 

  21. Bonfrer JM. Working group on tumor marker criteria (WGTMC). Tumour Biol. 1990;11(5):287–8.

    Article  PubMed  CAS  Google Scholar 

  22. Oikawa T, Kushuhara M, Ishikawa S, Hitomi J, Kono A, Iwanaga T, et al. Production of endothelin-1 and thrombomodulin by human pancreatic cancer cells. Br J Cancer. 1994;69(6):1059–64.

    Article  PubMed  CAS  Google Scholar 

  23. Senger DR, Van de Water L, Brown LF, Nagy JA, Yeo KT, Yeo TK, et al. Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Rev. 1993;12(3–4):303–24.

    Article  PubMed  CAS  Google Scholar 

  24. Papassotiriou J, Morgenthaler NG, Struck J, Alonso C, Bergmann A. Immunoluminometric assay for measurement of the C-terminal endothelin-1 precursor fragment in human plasma. Clin Chem. 2006;52(6):1144–51.

    Article  PubMed  CAS  Google Scholar 

  25. Liao XF, Yi JL, Li XR, Deng W, Yang ZF, Tian G. Angiogenesis in rabbit hepatic tumor after transcatheter arterial embolization. World J Gastroenterol. 2004;10(13):1885–9.

    PubMed  Google Scholar 

  26. von Marschall Z, Scholz A, Cramer T, Schafer G, Schirner M, Oberg K, et al. Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst. 2003;95(6):437–48.

    Article  Google Scholar 

  27. Grimshaw MJ. Endothelins and hypoxia-inducible factor in cancer. Endocr-Relat Cancer. 2007;14(2):233–44.

    Article  PubMed  CAS  Google Scholar 

  28. Kedzierski RM, Yanagisawa M. Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol. 2001;41:851–76.

    Article  PubMed  CAS  Google Scholar 

  29. Rossi GP, Seccia TM, Albertin G, Pessina AC. Measurement of endothelin: clinical and research use. Ann Clin Biochem. 2000;37(Pt 5):608–26.

    Article  PubMed  CAS  Google Scholar 

  30. Struck J, Morgenthaler NG, Bergmann A. Proteolytic processing pattern of the endothelin-1 precursor in vivo. Peptides. 2005;26(12):2482–6.

    Article  PubMed  CAS  Google Scholar 

  31. Brunner F, Stessel H, Watzinger N, Loffler BM, Opie LH. Binding of endothelin to plasma proteins and tissue receptors: effects on endothelin determination, vasoactivity, and tissue kinetics. FEBS Lett. 1995;373(1):97–101.

    Article  PubMed  CAS  Google Scholar 

  32. Ueda H, Tanaka H, Kida Y, Fukuchi H, Ichinose M. Adjuvant chemotherapy with tegafur/uracil administration after transcatheter arterial chemoembolization for advanced hepatocellular carcinoma. Oncol Rep. 2008;19(5):1355–61.

    PubMed  CAS  Google Scholar 

  33. Chung YL, Jian JJ, Cheng SH, Tsai SY, Chuang VP, Soong T, et al. Sublethal irradiation induces vascular endothelial growth factor and promotes growth of hepatoma cells: implications for radiotherapy of hepatocellular carcinoma. Clin Cancer Res. 2006;12(9):2706–15.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

The authors thank T.C. Linders and J.C.G.M. Buning-Kager for their excellent technical assistance with the immunoassays and Brahms AG (Hennigsdorf, Germany) for funding this research.

Author information

Authors and Affiliations

  1. Department of Clinical Chemistry, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands

    Catharina M. Korse & Johannes M. G. Bonfrer

  2. Department of Radiology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

    Warner Prevoo

  3. Department of Medical Oncology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

    Paul Baas & Babs G. Taal

Authors
  1. Catharina M. Korse
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Johannes M. G. Bonfrer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Warner Prevoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul Baas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Babs G. Taal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Catharina M. Korse.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Korse, C.M., Bonfrer, J.M.G., Prevoo, W. et al. Increase of angiogenic growth factors after hepatic artery embolization in patients with neuroendocrine tumours. Tumor Biol. 32, 647–652 (2011). https://doi.org/10.1007/s13277-011-0164-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-011-0164-7

Keywords

Search

Navigation