Expression of Angiogenic Factors in Myeloma Cells
To clarify the cellular biological roles of angiogenic factors in myeloma cells, we studied the gene expression of various angiogenic factors, including vascular endothelial growth factors (VEGFs), in 10 human myeloma cell lines (MMCLs) using the multiplex-reverse transcriptase-polymerase chain reaction (MP-RT-PCR). The VEGF-A secretion into culture medium, the effects of anti-VEGF-monoclonal antibody (MoAb) and interferon (IFN)-α on myeloma cells were also studied. The following results were obtained. (1) VEGF-A, -B, and -D were expressed in all the lines studied and that the expression levels of VEGF-A, and -B were significantly higher in the MMCLs than in the non-myelomatous hematological cell lines (nMCLs). Three out of ten MMCLs showed VEGF-C expression, but none of the nMCLs did. VEGF receptor -1 (VEGFR1) was expressed in all the lines, VEGF receptor-2 (VEGFR2) was found in three of the ten MMCLs, and two of the nMCLs. (2) VEGF-A production measured by the enzyme-linked immunosorbent assay (ELISA) was significantly higher in the MMCLs than in the nMCLs. (3) Anti-VEGF-MoAb resulted in growth inhibition in some myeloma cell lines. (4) IFN-α caused growth inhibition in KMS-21BM cells in vitro, but VEGF-A secretion increased. Based on these results, it is suggested that the angiogenic factors studied play important roles in myeloma cell proliferation, and that anti-angiogenic therapies may be useful not only for solid tumors but also for hematological malignancies, especially myelomas.