PURPOSE: Angiogenesis appears to be a prominent feature of many hematological disorders, particularly in multiple myeloma (MM). Progression in MM also involves secretion of the metaloproteinases (MMPs). In this study, the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and its receptor, in bone marrow trephine biopsy (TB) of thirty six MM patients before and after the treatment or during progression was examined. The MMP-2 secretion was assessed from the same patients. MATERIAL/ METHODS: Immunohistochemical staining of bone marrow specimens for angiogenic factors and microvessel density (MVD) and bone marrow aspirates for Western blot analysis of MMP-2 expression was performed. RESULTS: In active, untreated MM patients, we found statistically significant differences in the expression of angiogenic factors according to the patients after the anti-angiogenic treatment. We found statistical differences of the expression of angiogenic factors between the group of patients with a response after the treatment and the patients who had progression during the treatment. The data showed statistically significant decreased MVD after the treatment. The results showed statistically significant differences between initial secretion of MMP-2 in active, untreated MM patients and patients with a response after the treatment and patients with progression during the treatment. CONCLUSIONS: We showed that not only decreased expression of angiogenic cytokines is present after the anti-angiogenic treatment but also activity of MMP-2 in MM patients who responded to the treatment. Combination therapy with the inhibition of the activity of MMPs could represent an interesting therapeutical approach in MM.
PURPOSE: Angiogenesis appears to be a prominent feature of many hematological disorders, particularly in multiple myeloma (MM). Progression in MM also involves secretion of the metaloproteinases (MMPs). In this study, the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and its receptor, in bone marrow trephine biopsy (TB) of thirty six MM patients before and after the treatment or during progression was examined. The MMP-2 secretion was assessed from the same patients. MATERIAL/ METHODS: Immunohistochemical staining of bone marrow specimens for angiogenic factors and microvessel density (MVD) and bone marrow aspirates for Western blot analysis of MMP-2 expression was performed. RESULTS: In active, untreated MM patients, we found statistically significant differences in the expression of angiogenic factors according to the patients after the anti-angiogenic treatment. We found statistical differences of the expression of angiogenic factors between the group of patients with a response after the treatment and the patients who had progression during the treatment. The data showed statistically significant decreased MVD after the treatment. The results showed statistically significant differences between initial secretion of MMP-2 in active, untreated MM patients and patients with a response after the treatment and patients with progression during the treatment. CONCLUSIONS: We showed that not only decreased expression of angiogenic cytokines is present after the anti-angiogenic treatment but also activity of MMP-2 in MM patients who responded to the treatment. Combination therapy with the inhibition of the activity of MMPs could represent an interesting therapeutical approach in MM.
Authors: Gemma Shay; Marilena Tauro; Fulvio Loiodice; Paolo Tortorella; Daniel M Sullivan; Lori A Hazlehurst; Conor C Lynch Journal: Oncotarget Date: 2017-06-27