Angiogenesis is a crucial process in the progression of
multiple myeloma (MM).
Vascular endothelial growth factor (
VEGF) and
hepatocyte growth factor (HGF) are multifunctional
cytokines that potently stimulate angiogenesis including tumour neovascularization. Serum levels of
VEGF and HGF were measured in 52 patients with MM by
enzyme-linked
immunosorbent assay (ELISA). Serum levels of
VEGF and HGF were elevated in MM patients compared with healthy controls (
VEGF: mean 0.31 ng/ml and 0.08 ng/ml respectively, P < 0.01; HGF: mean 2.17 ng/ml and 0.45 ng/ml, respectively, P < 0.001). In serial samples taken after
chemotherapy, serum
VEGF and HGF levels were correlated with M-
protein levels. Serum levels of
VEGF were higher in patients with extramedullary
plasmacytomas than in patients without them (P < 0.05). They were also significantly higher in a group of patients who showed poor response to
chemotherapy (P < 0.01). Serum levels of HGF were higher in patients with complications such as anaemia, hypercalcaemia and
amyloidosis than in patients without these complications (P < 0.01, P < 0.05, P < 0.05 respectively). Both serum
VEGF and HGF levels were significant predictors of mortality (P = 0.01, P = 0.02, respectively, log-rank test). The present study demonstrated that serum levels of
VEGF and HGF are significantly elevated and dependent on the severity of MM, suggesting that measurement of
VEGF and HGF may be useful for assessing
disease progression and for predicting the response to
chemotherapy in MM patients.