Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 10/2014

01-10-2014 | Original Article – Clinical Oncology

Prognostic impact of angiopoietin-2 in multiple myeloma

Authors: Constantina A. Pappa, Michael G. Alexandrakis, Anna Boula, Aspasia Thanasia, Ioannis Konsolas, Athanasios Alegakis, George Tsirakis

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2014

Login to get access

Abstract

Purpose

Angiogenesis is an essential process for the expansion of multiple myeloma (MM). Angiopoietin-2 (Ang-2), Ang-1 and their receptor possess important roles in this procedure. The aim of the study was to measure serum levels of Ang-2 along with known markers of angiogenesis and to estimate their prognostic impact on the survival.

Methods

Bone marrow microvascular density (MVD), estimated by CD31, and circulating levels of known angiogenic factors Ang-2, interleukin-6, soluble CD105 and platelet-derived growth factor-AB, measured by ELISA, were measured in 77 newly diagnosed patients with active MM and in 57 of them who responded to chemotherapy.

Results

All measured parameters were increased in MM patients, were also increasing in advanced disease and decreased after effective treatment. Ang-2 correlated positively with the other angiogenic factors and MVD. Moreover, Ang-2 values above the median were accompanied by worse survival.

Conclusion

Ang-2 correlates strongly with the angiogenic process and its serum levels are importantly prognostic for survival, highlighting the role of angiopoietins pathway in the biology of MM.
Literature
go back to reference Agnelli L, Bicciato S, Mattioli M et al (2005) Molecular classification of multiple myeloma: a distinct transcriptional profile characterizes patients expressing CCND1 and negative for 14q32 translocations. J Clin Oncol 23:7296–7306PubMedCrossRef Agnelli L, Bicciato S, Mattioli M et al (2005) Molecular classification of multiple myeloma: a distinct transcriptional profile characterizes patients expressing CCND1 and negative for 14q32 translocations. J Clin Oncol 23:7296–7306PubMedCrossRef
go back to reference Anargyrou K, Terpos E, Vassilakopoulos TP et al (2008) Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib. Haematologica 93:451–454PubMedCrossRef Anargyrou K, Terpos E, Vassilakopoulos TP et al (2008) Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib. Haematologica 93:451–454PubMedCrossRef
go back to reference Bhaskar A, Gupta R, Vishnubhatla S et al (2013a) Angiopoietins as biomarker of disease activity and response to therapy in multiple myeloma. Leuk Lymphoma 54:1473–1478PubMedCrossRef Bhaskar A, Gupta R, Vishnubhatla S et al (2013a) Angiopoietins as biomarker of disease activity and response to therapy in multiple myeloma. Leuk Lymphoma 54:1473–1478PubMedCrossRef
go back to reference Bhaskar A, Gupta R, Sreenivas V et al (2013b) Synergistic effect of vascular endothelial growth factor and angiopoietin-2 on progression free survival in multiple myeloma. Leuk Res 37:410–415PubMedCrossRef Bhaskar A, Gupta R, Sreenivas V et al (2013b) Synergistic effect of vascular endothelial growth factor and angiopoietin-2 on progression free survival in multiple myeloma. Leuk Res 37:410–415PubMedCrossRef
go back to reference Dong X, Han ZC, Yang R (2007) Angiogenesis and antiangiogenic therapy in hematologic malignancies. Crit Rev Oncol Hematol 62:105–118PubMedCrossRef Dong X, Han ZC, Yang R (2007) Angiogenesis and antiangiogenic therapy in hematologic malignancies. Crit Rev Oncol Hematol 62:105–118PubMedCrossRef
go back to reference Duff SE, Li C, Garlang JM, Kumar S (2003) CD105 is important for angiogenesis: evidence and potential applications. FASEB J 17:984–992PubMedCrossRef Duff SE, Li C, Garlang JM, Kumar S (2003) CD105 is important for angiogenesis: evidence and potential applications. FASEB J 17:984–992PubMedCrossRef
go back to reference Giuliani N, Colla S, Lazzaretti M et al (2003) Proangiogenic properties of human myeloma cells: production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis. Blood 102:638–645PubMedCrossRef Giuliani N, Colla S, Lazzaretti M et al (2003) Proangiogenic properties of human myeloma cells: production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis. Blood 102:638–645PubMedCrossRef
go back to reference Holash J, Wiegand SJ, Yancopoulos GD (1999) New model of tumour angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene 118:5356–5362CrossRef Holash J, Wiegand SJ, Yancopoulos GD (1999) New model of tumour angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene 118:5356–5362CrossRef
go back to reference Loughna S, Sato TN (2001) Angiopoietin and Tie signalling pathways in vascular development. Matrix Biol 20:319–325PubMedCrossRef Loughna S, Sato TN (2001) Angiopoietin and Tie signalling pathways in vascular development. Matrix Biol 20:319–325PubMedCrossRef
go back to reference Maisonpierre PC, Suri C, Jones PF et al (1997) Angiopoietin-2, a natural antagonist for Tie-2 that disrupts in vivo angiogenesis. Science 277:55–60PubMedCrossRef Maisonpierre PC, Suri C, Jones PF et al (1997) Angiopoietin-2, a natural antagonist for Tie-2 that disrupts in vivo angiogenesis. Science 277:55–60PubMedCrossRef
go back to reference Mitsiades CS, Mitsiades NS, Munshi NC, Richardson PG, Anderson KC (2006) 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 42:1564–1573PubMedCrossRef Mitsiades CS, Mitsiades NS, Munshi NC, Richardson PG, Anderson KC (2006) 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 42:1564–1573PubMedCrossRef
go back to reference Papetti M, Herman IM (2001) Mechanism of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol 282:947–970CrossRef Papetti M, Herman IM (2001) Mechanism of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol 282:947–970CrossRef
go back to reference Pappa CA, Tsirakis G, Samiotakis P et al (2013a) Serum levels of angiopoietin-2 are associated with the growth of multiple myeloma. Cancer Invest 31:385–389PubMedCrossRef Pappa CA, Tsirakis G, Samiotakis P et al (2013a) Serum levels of angiopoietin-2 are associated with the growth of multiple myeloma. Cancer Invest 31:385–389PubMedCrossRef
go back to reference Pappa C, Alexandrakis M, Boula A et al (2013b) Emerging roles of endoglin/CD105 and angiogenic cytokines for disease development and progression in multiple myeloma patients. Hematol Oncol. doi:10.1002/hon.2044 Pappa C, Alexandrakis M, Boula A et al (2013b) Emerging roles of endoglin/CD105 and angiogenic cytokines for disease development and progression in multiple myeloma patients. Hematol Oncol. doi:10.​1002/​hon.​2044
go back to reference Plank MJ, Sleeman BD, Jones PF (2004) The role of the angiopoietins in tumour angiogenesis. Growth Factors 22:1–11PubMedCrossRef Plank MJ, Sleeman BD, Jones PF (2004) The role of the angiopoietins in tumour angiogenesis. Growth Factors 22:1–11PubMedCrossRef
go back to reference Quartarone E, Alonci A, Allegra A et al (2006) Differential levels of soluble angiopoietin-2 and Tie-2 in patients with haematological malignancies. Eur J Haematol 77:480–485PubMedCrossRef Quartarone E, Alonci A, Allegra A et al (2006) Differential levels of soluble angiopoietin-2 and Tie-2 in patients with haematological malignancies. Eur J Haematol 77:480–485PubMedCrossRef
go back to reference Scharpfenecker M, Fiedler U, Reiss Y, Augustin HG (2005) The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through and internal autocrine loop mechanism. J Cell Sci 118:771–780PubMedCrossRef Scharpfenecker M, Fiedler U, Reiss Y, Augustin HG (2005) The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through and internal autocrine loop mechanism. J Cell Sci 118:771–780PubMedCrossRef
go back to reference Sezer O, Niemoller K, Eucker J et al (2000) Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma. Ann Hematol 79:574–577PubMedCrossRef Sezer O, Niemoller K, Eucker J et al (2000) Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma. Ann Hematol 79:574–577PubMedCrossRef
go back to reference Terpos E, Anargyrou K, Katodritou E et al (2012) Circulating angiopoietin-1 to angiopoietin-2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents. Int J Cancer 130:735–742PubMedCrossRef Terpos E, Anargyrou K, Katodritou E et al (2012) Circulating angiopoietin-1 to angiopoietin-2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents. Int J Cancer 130:735–742PubMedCrossRef
go back to reference Tsirakis G, Pappa CA, Spanoudakis M et al (2012a) Clinical significance of sCD105 in angiogenesis and disease activity in multiple myeloma. Eur J Int Med 23:368–373CrossRef Tsirakis G, Pappa CA, Spanoudakis M et al (2012a) Clinical significance of sCD105 in angiogenesis and disease activity in multiple myeloma. Eur J Int Med 23:368–373CrossRef
go back to reference Tsirakis G, Pappa C, Kanellou P et al (2012b) Role of platelet-derived growth factor-AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma. Hematol Oncol 30:131–136PubMedCrossRef Tsirakis G, Pappa C, Kanellou P et al (2012b) Role of platelet-derived growth factor-AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma. Hematol Oncol 30:131–136PubMedCrossRef
go back to reference Uneda S, Matsuno F, Sonoki T et al (2003) Expression of vascular endothelial factor and angiopoietin-2 in myeloma cells. Haematologica 88:113–115PubMed Uneda S, Matsuno F, Sonoki T et al (2003) Expression of vascular endothelial factor and angiopoietin-2 in myeloma cells. Haematologica 88:113–115PubMed
go back to reference Yancopoulos GD, Davis S, Gale NW et al (2000) Vascular-specific growth factors and blood vessel formation. Nature 407:242–248PubMedCrossRef Yancopoulos GD, Davis S, Gale NW et al (2000) Vascular-specific growth factors and blood vessel formation. Nature 407:242–248PubMedCrossRef
Metadata
Title
Prognostic impact of angiopoietin-2 in multiple myeloma
Authors
Constantina A. Pappa
Michael G. Alexandrakis
Anna Boula
Aspasia Thanasia
Ioannis Konsolas
Athanasios Alegakis
George Tsirakis
Publication date
01-10-2014
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 10/2014
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-014-1731-2

Other articles of this Issue 10/2014

Journal of Cancer Research and Clinical Oncology 10/2014 Go to the issue