Skip to main content

Advertisement

Log in

Circulating serum levels of IL-20 in multiple myeloma patients: its significance in angiogenesis and disease activity

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Angiogenesis is an important hallmark in multiple myeloma (MM) pathogenesis, with the participation of various versatile molecules. Interleukin-20 (IL-20) is a pro-inflammatory cytokine with diverse angiogenic properties. Our purpose was to estimate the possible impact of IL-20 on MM angiogenesis and disease activity. We measured serum levels of IL-20 along with levels of vascular endothelial growth factor (VEGF), basic-fibroblast growth factor and angiopoietin 2 in 58 active MM myeloma patients, in 32 of them who responded to bortezomib-based therapy and in 20 controls. We also measured bone marrow microvasclular density (MVD) by immunohistochemical method. Serum levels of all cytokines and bone marrow MVD were higher in active MM patients compared to controls and responders to bortezomib-based therapy (p < 0.001 in all cases). They were also in parallel with International Staging System stages (p < 0.001 for all cases). Serum levels of IL-20 correlated positively with levels of angiogenic cytokines and bone marrow MVD (p < 0.01 for MVD, p < 0.002 for VEGF and p < 0.001 for the other cases). Our results strongly suggest that serum IL-20 concentrations participate actively in the pathophysiology of MM progression. Therefore, it could be used as an indicator of the disease progression and angiogenesis processes.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Sezer O, Niemoller K, Eucker J, Jacob C, Kaufmann O, Zavrski I, Dietel M, Possinger K. Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma. Ann Hematol. 2000;79:574–7.

    Article  CAS  PubMed  Google Scholar 

  2. Mitsiades CS, Mitsiades NS, Munshi NC, Richardson PG, Anderson KC. The role of the bone marrow microenvironment in the pathophysiology and therapeutic management of multiple myeloma: interplay of growth factors, their receptors and stromal interactions. Eur J Cancer. 2006;42:1564–73.

    Article  CAS  PubMed  Google Scholar 

  3. Vacca A, Ria R, Ribatti D, et al. A paracrine loop in the vascular endothelial growth factor pathway triggers tumor angiogenesis and growth in multiple myeloma. Haematologica. 2003;88:176–85.

    CAS  PubMed  Google Scholar 

  4. Dankbar B, Padro T, Leo R, et al. Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood. 2000;95:2630–6.

    CAS  PubMed  Google Scholar 

  5. Ribatti D, Vacca A, Rusnati M, Presta M. The discovery of basic fibroblastic growth factor/fibroblast growth factor-2 and its role in haematological malignancies. Cytokine Growth Factor Rev. 2007;18:327–34.

    Article  CAS  PubMed  Google Scholar 

  6. Scharpfenecker M, Fiedler U, Reiss Y, Augustin HG. The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through and internal autocrine loop mechanism. J Cell Sci. 2005;118:771–80.

    Article  CAS  PubMed  Google Scholar 

  7. Hsu YH, Chang MS. The therapeutic potential of anti-interleukin-20 monoclonal antibody. Cell Transplant. 2014;23:631–9.

    Article  PubMed  Google Scholar 

  8. Chen WY. Chang MS.IL-20 is regulated by hypoxia-inducible factor and up-regulated after experimental ischemic stroke. J Immunol. 2009;182:5003–12.

    Article  CAS  PubMed  Google Scholar 

  9. Chen WY, Cheng BC, Jiang NJ, Hsieh MY, Chang MS. IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice. Atherioscler Thromb Vasc Biol. 2006;26:2090–5.

    Article  CAS  Google Scholar 

  10. Blumberg H, Conklin D, Xu WF, Grossmann A, Brender T, Carollo S, Eagan M, Foster D, Haldeman BA, Hammond A, Haugen H, Jelinek K, Kelly JD, Madden K, Mauer MF, Parrish-Novak J, Prunkard D, Sexson S, Sprecher C, Waggie K, West J, Whitmore TE, Yao L, Kuechle MK, Dale BA, Chandrasekher YA. Interleukin 20:discovery, receptor identification, and role in epidermal function. Cell. 2001;104:9–19.

    Article  CAS  PubMed  Google Scholar 

  11. Wei CC, Hsu YH, Li HH, Wang YC, Hsieh MY, Chen WY, Hsing CH, Chang MS. Detection of IL-20: biological functions and clinical implications. J Biomed Sci. 2006;13:601–12.

    Article  CAS  PubMed  Google Scholar 

  12. Tsirakis G, Pappa CA, Spanoudakis M, Chochlakis D, Alegakis A, Psarakis FE, Stratinaki M, Stathopoulos EN, Alexandrakis MG. Clinical significance of sCD105 in angiogenesis and disease activity in multiple myeloma. Eur J Int Med. 2012;23:368–73.

    Article  CAS  Google Scholar 

  13. Baird AM, Gray SG, O’Byrne KJ. IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF. Eur J Cancer. 2011;47:1908–18.

    Article  CAS  PubMed  Google Scholar 

  14. Heuzé-Vourc’h N, Liu M, Dalwadi H, Baratelli FE, Zhu L, Goodglick L, Põld M, Sharma S, Ramirez RD, Shay JW, Minna JD, Strieter RM, Dubinett SM. IL-20, an anti-angiogenic cytokine that inhibits COX-2 expression. Biochem Biophys Res Commun. 2005;29(333):470–5.

    Article  Google Scholar 

  15. Hsieh MY, Chen WY, Jiang MJ, Cheng BC, Huang TY, Chang MS. Interleukin-20 promotes angiogenesis in a direct and indirect manner. Genes Immun. 2006;7:234–42.

    Article  CAS  PubMed  Google Scholar 

  16. Tritsaris K, Myren M, Ditlev SB, Hübschmann MV, van der Blom I, Hansen AJ, Olsen UB, Cao R, Zhang J, Jia T, Wahlberg E, Dissing S, Cao Y. IL-20 is an arteriogenic cytokine that remodels collateral networks and improves functions of ischemic hind limbs. Proc Natl Acad Sci USA. 2007;104:15364–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Buschmann I, Heil M, Jost M, Schaper W. Influence of inflammatory cytokines on arteriogenesis. Microcirculation. 2003;10:371–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they do not have any conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. G. Alexandrakis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alexandrakis, M.G., Pappa, C.A., Kokonozaki, M. et al. Circulating serum levels of IL-20 in multiple myeloma patients: its significance in angiogenesis and disease activity. Med Oncol 32, 42 (2015). https://doi.org/10.1007/s12032-015-0488-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-015-0488-z

Keywords

Navigation