Anti-Myeloma Effects of a Novel Synthetic Retinoid Am80 (Tamibarotene) through Inhibition of Angiogenesis.

In multiple myeloma (MM), the interaction between myeloma cells and bone marrow microenvironment has an important role in the pathogenesis of MM. We first examined the inducing effect of myeloma cells on migration of human umbilical vein vascular endothelial cells (HUVECs). Myeloma cell lines produced varying amounts of vascular endothelial growth factor (VEGF), and migration of HUVECs was induced by co-culture with myeloma cells. We next examined the inhibitory effect of a novel synthetic retinoid Am80 (Tamibarotene) on both myeloma cells and HUVECs. Am80 remarkably inhibited the growth of HUVECs stimulated by VEGF and blocked migration of HUVECs by co-cultured myeloma cells. In addition, VEGF-induced formation of tube-like structures in vitro and neovascularization in mouse corneas were significantly inhibited by Am80. Am80 downregulated both interleukin-6 (IL-6) and IL-6 receptor, and blocked VEGF-induced phosphorylation of VEGF receptor. Furthermore, microarray analysis suggested that Am80 has immunomodulatory effects on myeloma cells. These findings demonstrate that Am80 might be a useful therapeutic agent against MM.