ABSTRACT
The aim of the study was to evaluate serum levels of FLT3-ligand (FLT3-L), a soluble molecule in bone marrow (BM), participating actively in hematopoiesis, in relation with angiogenic factors in multiple myeloma (MM) patients. We measured, in 70 patients with active MM and in 38 of them who responded to conventional therapy, serum levels of FLT3-L, along with known angiogenic factors, such as VEGF, endoglin, TNF-alpha and HGF (with ELISA) and BM microvascular density (MVD), estimating the immunohistochemical expression of CD31. All pre-treatment values were higher in active MM patients compared to controls (p<0.001 for all cases), in parallel with both International Staging System and Durie-Salmon stages (p<0.001 for all cases). Moreover, levels of FLT3-L correlated positively with all soluble angiogenic factors, as well with MVD (p<0.0001 for all cases). Post-treatment values of FLT3-L decreased significantly in responders to therapy (p<0.001). The underlying relation of MM angiogenesis with FLT3-L may result from the fact that BM microvasculature is a major source of FLT3-L, both in BM niche and probably in peripheral blood. Our results suggest that serum levels of FLT3-L may be used as angiogenic marker in MM patients.
Subject(s)
Membrane Proteins/physiology , Multiple Myeloma/blood supply , Neoplasm Proteins/physiology , Neovascularization, Pathologic/metabolism , Aged , Aged, 80 and over , Antigens, CD/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/blood supply , Bortezomib/administration & dosage , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Endoglin , Female , Hepatocyte Growth Factor/blood , Humans , Male , Melphalan/administration & dosage , Membrane Proteins/blood , Microvessels/pathology , Middle Aged , Multiple Myeloma/drug therapy , Neoplasm Proteins/blood , Neoplasm Staging , Prednisone/administration & dosage , Receptors, Cell Surface/blood , Tumor Necrosis Factor-alpha/analysis , Vascular Endothelial Growth Factor A/bloodABSTRACT
Angiogenesis is an important hallmark in multiple myeloma (MM) pathogenesis, with the participation of various versatile molecules. Interleukin-20 (IL-20) is a pro-inflammatory cytokine with diverse angiogenic properties. Our purpose was to estimate the possible impact of IL-20 on MM angiogenesis and disease activity. We measured serum levels of IL-20 along with levels of vascular endothelial growth factor (VEGF), basic-fibroblast growth factor and angiopoietin 2 in 58 active MM myeloma patients, in 32 of them who responded to bortezomib-based therapy and in 20 controls. We also measured bone marrow microvasclular density (MVD) by immunohistochemical method. Serum levels of all cytokines and bone marrow MVD were higher in active MM patients compared to controls and responders to bortezomib-based therapy (p < 0.001 in all cases). They were also in parallel with International Staging System stages (p < 0.001 for all cases). Serum levels of IL-20 correlated positively with levels of angiogenic cytokines and bone marrow MVD (p < 0.01 for MVD, p < 0.002 for VEGF and p < 0.001 for the other cases). Our results strongly suggest that serum IL-20 concentrations participate actively in the pathophysiology of MM progression. Therefore, it could be used as an indicator of the disease progression and angiogenesis processes.
