Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma

Angiogenesis is a crucial process in growth and progression of cancer and t here is growing evidence that neovascularisation is important in hematologi cal malignancies. Since an increased angiogenic potential has been identifi ed in multiple myeloma, we simultaneously measured circulating serum levels of the cytokines bFGF, VEGF, HGF and IL-6 by ELISA in 67 patients with mul tiple myeloma or monoclonal gammopathies of undetermined significance (MGUS ) and in 20 controls. Median values of bFGF were 4.7 pg/ml in healthy volun teers, 6.2 in MGUS, 6.3 in myeloma stage I, 13.4 in stage II and 21.7 in st age III. Myeloma patients had significantly higher bFGF serum levels than c ontrols (p < 0.001). Pretreatment bFGF levels differed significantly in the Salmon and Durie stages I-III (p = 0.02) and were significantly elevated i n stage II-III compared to stage I myeloma (p = 0.02). In patients respondi ng to chemotherapy according to the CLMTF criteria, a significant decrease in serum bFGF, VEGF and HGF levels occurred (median pretreatment values for bFGF 23.9 pg/ml, post-treatment 6.5 pg/ml; p < 0.001, for VEGF 223 pg/ml v ersus 105 pg/ml; p = 0.02 and for HGF 1429 pg/ml versus 1077 pg/ml, p = 0.0 2, respectively). In 11 patients who did not achieve a remission, there was no significant decrease in bFGF, VEGF and HGF levels. These data show that myeloma in stages II and III is associated with an increase in serum bFGF concentrations and give the first report that effective chemotherapy is acc ompanied by a significant decrease in the angiogenic factors bFGF, VEGF and HGF, while no decrease of these factors could be found in nonresponders.