ADVANCES IN THERAPY, vol.23, no.4, pp.635-645, 2006 (SCI-Expanded)
Angiogenesis is a process that plays an important role in the growth and progression of cancer; growing evidence suggests that neovascularization is important in hematologic malignancies. Increased angiogenic potential has been identified in multiple myeloma (MM). In this study, investigators simultaneously measured the levels of hepatocyte growth factor (HGF), platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor-alpha (TGF-alpha) through enzyme-linked immunosorbent assay in the bone marrow (BM) and peripheral blood (PB) of 30 patients with MM and 10 healthy controls. Differences in HGF values in BM sera were significant (P=.001) between patients and controls. In detailed analyses of HGF, PDGF-AB, and TGF-alpha, according to disease stage, a significant correlation was found between disease stage and BM HGF (P=.047), BM TGF-alpha (P=.021), and PB PDGF-AB (P=.006), respectively. When correlations between all other parameters were analyzed, significance was noted between PB TGF-alpha and lactate dehydrogenase (P=.02), PB TGF-alpha and PB HGF (P=.002), BM TGF-alpha and CD38 (P=.046), BM TGF-alpha and BM HGF (P=.000), BM TGF-alpha and BM PDGF-AB (P=.048), BM HGF and PB HGF (P=.044), and BM PDGF-AB and PB PDGF-AB (P=.000). BM HGF levels had a significant effect on overall survival, with disease severity assessed in terms of disease stage (P=.001 8, log-rank test). These data show that in patients with MM, high levels of BM HGF, BM TGF-alpha, and PB PDGF-AB were associated with advanced disease stage; in addition, HGF played a significant role in disease processing and was related to disease severity. These findings have also led to the concept of a symbiotic relationship between the growth of myeloma cells and HGF, TGF-alpha, and PDGF-AB in BM.