Hypoxia and Activated VEGF/Receptor Pathway in Multiple Myeloma

Intensified angiogenic pathways are associated with poor prognosis and resistance of multiple myeloma (MM) cells to therapy. The links of the VEGF pathway with the hypoxia inducible factor (HIF) expression in MM are herein investigated. The vascular density (VD) and the HIF/VEGF/VEGF-receptor expres...

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Bibliographic Details
Published in:Anticancer research 2010-07, Vol.30 (7), p.2831-2836
Main Authors: GIATROMANOLAKI, Alexandra, BAI, Maria, MARGARITIS, Dimitrios, BOURANTAS, Konstantinos L, KOUKOURAKIS, Michael I, SIVRIDIS, Efthimios, GATTER, Kevin C
Format: Article
Language:English
Subjects:
Basic Helix-Loop-Helix Transcription Factors - metabolism
Biological and medical sciences
Cell Hypoxia - physiology
Humans
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Immunodeficiencies. Immunoglobulinopathies
Immunoglobulinopathies
Immunohistochemistry
Immunopathology
Medical sciences
Multiple Myeloma - blood supply
Multiple Myeloma - metabolism
Multiple Myeloma - pathology
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - pathology
Phosphorylation
Receptors, Vascular Endothelial Growth Factor - metabolism
Tumors
Vascular Endothelial Growth Factor A - metabolism
Vascular Endothelial Growth Factor Receptor-2 - metabolism
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Summary:Intensified angiogenic pathways are associated with poor prognosis and resistance of multiple myeloma (MM) cells to therapy. The links of the VEGF pathway with the hypoxia inducible factor (HIF) expression in MM are herein investigated. The vascular density (VD) and the HIF/VEGF/VEGF-receptor expression in the bone marrows of 106 MM cases were studied using immunohistochemistry. HIF1alpha and HIF2alpha were expressed strongly in 33% and 13.2% of the cases, respectively. VEGFR and the phosphorylated (active) form of VEGFR2/KDR receptors were up-regulated in 42.5% and 36.8% of cases, respectively. Both HIF1alpha and HIF2alpha were significantly linked with high VD and VEGF expression. Moreover, the expression of the phosphorylated (active) form of VEGFR2/KDR was significantly linked with VEGF and HIF1alpha expression. The HIF/VEGF/VEGF-receptor pathway is up-regulated in approximately 40% of MM cases and linked with increased angiogenesis. Survival analysis in 37 evaluable patients showed a significantly worse prognosis in cases with high VD. HIFs and VEGF are up-regulated in a significant percentage of MM and are strongly related to each other. Targeting HIFs and the VEGF/receptor autocrine loop may prove of importance in the treatment of the disease.
ISSN:0250-7005
1791-7530