, Volume 20, Issue 4, pp 443–462 | Cite as

Endothelial progenitor cells in multiple myeloma neovascularization: a brick to the wall

  • Maria Margarida Tenreiro
  • Maria Leonor Correia
  • Maria Alexandra BritoEmail author
Review Paper


Multiple myeloma (MM) is characterized by the clonal expansion of plasma cells in the bone marrow that leads to events such as bone destruction, anaemia and renal failure. Despite the several therapeutic options available, there is still no effective cure, and the standard survival is up to 4 years. The evolution from the asymptomatic stage of monoclonal gammopathy of undetermined significance to MM and the progression of the disease itself are related to cellular and molecular alterations in the bone marrow microenvironment, including the development of the vasculature. Post-natal vasculogenesis is characterized by the recruitment to the tumour vasculature of bone marrow progenitors, known as endothelial progenitor cells (EPCs), which incorporate newly forming blood vessels and differentiate into endothelial cells. Several processes related to EPCs, such as recruitment, mobilization, adhesion and differentiation, are tightly controlled by cells and molecules in the bone marrow microenvironment. In this review, the bone marrow microenvironment and the mechanisms associated to the development of the neovasculature promoted by EPCs are discussed in detail in both a non-pathological scenario and in MM. The latest developments in therapy targeting the vasculature and EPCs in MM are also highlighted. The identification and characterization of the pathways relevant to the complex setting of MM are of utter importance to identify not only biomarkers for an early diagnosis and disease progression monitoring, but also to reveal intervention targets for more effective therapy directed to cancer cells and the endothelial mediators relevant to neovasculature development.


Multiple myeloma Monoclonal gammopathy of undetermined significance Bone marrow Angiogenesis Vasculogenesis Endothelial progenitor cells 



The authors thank the Portuguese Foundation for Science and Technology, Portugal, for the award of the Strategic Project to iMed.ULisboa (UID/DTP/04138/2013).


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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Maria Margarida Tenreiro
    • 1
  • Maria Leonor Correia
    • 2
  • Maria Alexandra Brito
    • 1
    • 2
    Email author
  1. 1.Research Institute for Medicines (iMed.ULisboa), Faculty of PharmacyUniversidade de LisboaLisbonPortugal
  2. 2.Department of Biochemistry and Human Biology, Faculty of PharmacyUniversidade de LisboaLisbonPortugal

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