TY - JOUR
T1 - Angiopoietin-2 in Bone Marrow milieu promotes Multiple Myeloma-associated angiogenesis
AU - Belloni, Daniela
AU - Marcatti, Magda
AU - Ponzoni, Maurilio
AU - Ciceri, Fabio
AU - Veschini, Lorenzo
AU - Corti, Angelo
AU - Caligaris Cappio, Federico
AU - Ferrarini, Marina
AU - Ferrero, Elisabetta
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Angiopoietin-2
KW - Bone Marrow microenvironment
KW - Endothelial cells
KW - Multiple Myeloma
UR - http://www.scopus.com/inward/record.url?scp=84916886858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84916886858&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2014.10.017
DO - 10.1016/j.yexcr.2014.10.017
M3 - Article
C2 - 25447443
AN - SCOPUS:84916886858
VL - 330
SP - 1
EP - 12
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -