Angiopoietin-2 in Bone Marrow milieu promotes Multiple Myeloma-associated angiogenesis

Daniela Belloni, Magda Marcatti, Maurilio Ponzoni, Fabio Ciceri, Lorenzo Veschini, Angelo Corti, Federico Caligaris Cappio, Marina Ferrarini, Elisabetta Ferrero

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Angiopoietin-2 (Ang-2) is involved in angiogenesis in both solid and hematological malignancies. In Multiple Myeloma (MM), serum Ang-2 correlates with disease progression and response to therapy. To address the patho-physiologic role of Ang-2 in MM associated angiogenesis, we used sera from patients with active MM, which contained significantly higher levels of the molecule, compared to those from patients with smoldering MM and Monoclonal Gammopathy of Undetermined Significance. MM Bone Marrow (BM) sera with high Ang-2 concentration specifically contributed to endothelial cell (EC) activation, while Ang-1 containing sera maintained EC stabilization. The functional dichotomy of Ang-1 and Ang-2 was confirmed by the triggering of distinctive signaling pathways down-stream the common Tie-2 receptor, i.e., the Akt or the ERK- phosphorylation pathway. Notably, Ang-2 but not VEGF serum levels correlated with BM micro-vessel density, further underscoring the key role of Ang-2 in angiogenesis. Western Blot, RT-PCR and immunocytochemistry identified MMEC as the major source of Ang-2, at variance with MM cells and CD14(+) BM monocytes. These data suggest that Ang-2 produced in the BM milieu may contribute to MM angiogenesis and suggest that the molecule can be further exploited both as angiogenesis biomarker and as a potential therapeutic target.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalExperimental Cell Research
Volume330
Issue number1
Early online date24 Oct 2014
DOIs
Publication statusPublished - 1 Jan 2015

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiopoietin-1
  • Angiopoietin-2
  • Bone Marrow
  • Case-Control Studies
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Middle Aged
  • Multiple Myeloma
  • Neovascularization, Pathologic
  • Receptor, TIE-2
  • Vascular Endothelial Growth Factor A
  • Journal Article
  • Research Support, Non-U.S. Gov't

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