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Interrelationship between angiogenesis, inflammation and oxidative stress in Indian patients with multiple myeloma

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Abstract

Background

Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal population of plasma cells in the bone marrow (BM). A variety of angiogenic factors, proteases, reactive oxygen species and inflammatory cytokines induce the formation of an extensive and suitable BM microenvironment. Previous studies have established the importance of angiogenic factors, inflammatory molecules and oxidative stress in MM but their interplay and effect on each other are not being taken together.

Methods

Circulatory levels of VEGF, angiopoietin-2 (Ang-2), IL-6 and TNF-α along with the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were investigated in 112 subjects including 62 MM patients and 50 healthy controls. Inter-stage analysis was done to evaluate the association of these molecules with the severity of disease. Pearson correlation was determined to find interrelationship, if any, between these molecules.

Results

We have observed elevated levels of VEGF, Ang-2, IL-6, TNF-α and decreased activity of SOD, GPx in MM patients in comparison to controls. All these molecules also showed a trend with the severity of disease. We have found strong association between these factors upon their correlation and regression analysis.

Conclusion

This study is a step toward understanding the indepth contribution of angiogenesis, inflammation and oxidative stress together in making BM microenvironment suitable for growth, survival and proliferation of malignant plasma cells in MM.

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References

  1. Palumbo A, Anderson K. Multiple Myeloma. N Engl J Med. 2011;364:1046–60.

    Article  CAS  PubMed  Google Scholar 

  2. Badjatia N, Satyam A, Singh P, Seth A, Sharma A. Altered antioxidant status and lipid peroxidation in Indian patients with urothelial bladder carcinoma. Urol Oncol. 2010;28:360–7.

    Article  CAS  PubMed  Google Scholar 

  3. Sharma A, Rajappa M, Saxsena A, Sharma M. Antioxidant status in advanced cervical cancer patients undergoing neoadjuvant chemoradiation. Br J Biomed Sci. 2007;64:23–7.

    CAS  PubMed  Google Scholar 

  4. Jo M, Nishikawa T, Nakajima T, Okada Y, Yamaguchi K, Mitsuyoshi H, et al. Oxidative stress is closely associated with tumor angiogenesis of hepatocellular carcinoma. J Gastroenterol. 2011;46:809–21.

    Article  CAS  PubMed  Google Scholar 

  5. Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006;12:235–9.

    Article  CAS  PubMed  Google Scholar 

  6. Skuli N, Majmundar AJ, Krock BL, Mesquita RC, Mathew LK, Quinn ZL, et al. Endothelial HIF-2α regulates murine pathological angiogenesis and revascularization processes. J Clin Invest. 2012;122:1427–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Giatromanolaki A, Bai M, Margaritis D, Bourantas KL, Koukourakis MI, Sivridis E, et al. Hypoxia and activated VEGF/receptor pathway in multiple myeloma. Anticancer Res. 2010;30:2831–6.

    CAS  PubMed  Google Scholar 

  8. Angelo LS, Kurzrock R. Vascular endothelial growth factor and its relationship to inflammatory mediators. Clin Cancer Res. 2007;13:2825–30.

    Article  CAS  PubMed  Google Scholar 

  9. Valkovic T, Babarovic E, Lucin K, Stifter S, Aralica M, Pecanic S, et al. Plasma levels of osteopontin and vascular endothelial growth factor in association with clinical features and parameters of tumor burden in patients with multiple myeloma. Biomed Res Int. 2014;2014:513170.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Pappa CA, Alexandrakis MG, Boula A, Thanasia A, Konsolas I, Alegakis A, et al. Prognostic impact of angiopoietin-2 in multiple myeloma. J Cancer Res Clin Oncol. 2014;140:1801–5.

    Article  CAS  PubMed  Google Scholar 

  11. Lobov IB, Brooks PC, Lang RA. Angiopoietin-2 displays the VEGF-dependent modulation of capillary structure and endothelial survival in vitro. Proc Natl Acad Sci. 2009;99:11205–10.

    Article  Google Scholar 

  12. Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999;284:1994–8.

    Article  CAS  PubMed  Google Scholar 

  13. Brigelius-Flohe R, Kipp A. Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta. 1990;1790:1555–68.

    Article  Google Scholar 

  14. Tewari A, Mahendru V, Sinha A, Bilotta F. Antioxidants: the new frontier for translational research in cerebroprotection. J Anaesthesiol Clin Pharmacol. 2014;30:160–71.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Gangemi S, Allegra A, Alonci A, Cristani M, Russo S, Speciale A, et al. Increase of novel biomarkers for oxidative stress in patients with plasma cell disorders and in multiple myeloma patients with bone lesions. Inflamm Res. 2012;61:1063–7.

    Article  CAS  PubMed  Google Scholar 

  16. Goswami B, Rajappa M, Sharma M, Sharma A. Inflammation: its role and interplay in the development of cancer, with special focus on gynecological malignancies. Int J Gynecol Cancer. 2008;18:591–9.

    Article  CAS  PubMed  Google Scholar 

  17. Mehtap O, Atesoglu EB, Tarkun P, Hacihanefioglu A, Dolasik I, Musul MM. IL-21 and other serum proinflammatory cytokine levels in patients with multiple myeloma at diagnosis. J Postgrad Med. 2014;60:141–4.

    Article  CAS  PubMed  Google Scholar 

  18. Sharma A, Tripathi M, Satyam A, Kumar L. Study of antioxidant levels in patients with multiple myeloma. Leuk Lymphoma. 2009;50:691–3.

    Article  Google Scholar 

  19. Rajashekhar G, Willuweit A, Patterson CE, Sun P, Hilbig A, Breier G, et al. Continuous endothelial cell activation increases angiogenesis: evidence for the direct role of endothelium linking angiogenesis and inflammation. J Vasc Res. 2006;43:193–204.

    Article  PubMed  Google Scholar 

  20. West XZ, Malinin NL, Merkulova AA, Tischenko M, Kerr BA, Borden EC, et al. Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands. Nature. 2010;467:972–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Fraisl P, Mazzone M, Schmidt T, Carmeliet P. Regulation of angiogenesis by oxygen and metabolism. Dev Cell. 2009;16:167–79.

    Article  CAS  PubMed  Google Scholar 

  22. Joshi S, Khan R, Sharma M, Kumar L, Sharma A. Angiopoietin-2: a potential novel diagnostic marker in multiple myeloma. Clin Biochem. 2011;44:590–5.

    Article  CAS  PubMed  Google Scholar 

  23. Khan R, Sharma M, Kumar L, Husain SA, Sharma A. Interrelationship and expression profiling of cyclooxygenase and angiogenic factors in Indian patients with multiple myeloma. Ann Hematol. 2013;92:101–9.

    Article  CAS  PubMed  Google Scholar 

  24. Alexandrakis MG, Passam FH, Boula A, Christophoridou A, Aloizos G, Roussou P, et al. Relationship between circulating serum soluble interleukin-6 receptor and the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in multiple myeloma. Ann Hematol. 2003;82:19–23.

    CAS  PubMed  Google Scholar 

  25. Alexandrakis MG, Pappa CA, Miyakis S, Sfiridaki A, Kafousi M, Alegakis A, et al. Serum interleukin-17 and its relationship to angiogenic factors in multiple myeloma. Eur J Intern Med. 2006;17:412–6.

    Article  CAS  PubMed  Google Scholar 

  26. Dulak J, Tomala K, Loboda A, Jozkowicz A. Nitric oxide-dependent synthesis of vascular endothelial growth factor is impaired by high glucose. Life Sci. 2004;75:2573–86.

    Article  CAS  PubMed  Google Scholar 

  27. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20:1126–67.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Chen JX, Chen Y, DeBusk L, Lin W, Lin PC. A Dual functional roles of Tie-2/angiopoietin in TNF-alpha-mediated angiogenesis. Am J Physiol. 2004;287:187–95.

    Article  Google Scholar 

  29. Faller S, Spassov SG, Zimmermann KK, Ryter SW, Buerkle H, Loop T, et al. Hydrogen sulfide prevents hyperoxia-induced lung injury by downregulating reactive oxygen species formation and angiopoietin-2 release. Curr Pharm Des. 2013;19:2715–21.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We acknowledge the Indian Council of Medical Research, New Delhi, India, for providing monetary support to carry out this study. We would like to thank Dr. Guresh Kumar, Dept of Biostatistics, AIIMS, New Delhi for statistical analysis of data.

Conflict of interest

The authors declare that there is no conflict of interest.

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Author notes

    Authors and Affiliations

    1. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India

      S. Joshi, N. Gupta, R. Khan, R. Kumar & A. Sharma

    2. Department of Radiation Oncology, Maulana Azad Medical College, New Delhi, India

      M. Sharma

    3. Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

      L. Kumar

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    1. S. Joshi
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    7. A. Sharma
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    Corresponding author

    Correspondence to A. Sharma.

    Additional information

    S. Joshi, N. Gupta and R. Khan contributed equally.

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    Joshi, S., Gupta, N., Khan, R. et al. Interrelationship between angiogenesis, inflammation and oxidative stress in Indian patients with multiple myeloma. Clin Transl Oncol 18, 132–137 (2016). https://doi.org/10.1007/s12094-015-1344-5

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    • DOI: https://doi.org/10.1007/s12094-015-1344-5

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