Establishment of myeloma cell lines and biotechnological study on the regulatory mechanisms of myeloma cell growth.

由于骨髓基质细胞在骨髓瘤细胞的生长中起着重要的作用，我们使用基质细胞中的巨噬细胞作为饲养层来建立骨髓瘤细胞系。已经建立了6种以上的骨髓瘤细胞系。然后，将这些细胞系用于骨髓瘤细胞生长的分析，得到以下结果。1)巨噬细胞对骨髓瘤细胞的生长有积极作用，对建立骨髓瘤细胞系有重要作用。2)骨髓瘤细胞对IL-6和IL-1的增殖反应。巨噬细胞分泌的IL-6主要介导刺激作用。i 3)以巨噬细胞为饲养层，建立了6株骨髓瘤细胞株，4株骨髓瘤细胞株体外维持3-9个月。4)两种骨髓源性细胞系的增殖完全依赖于巨噬细胞或IL-6。然而，4种髓外病变来源的细胞系自发增殖。5)两种骨髓瘤细胞系ILKM3和KM4在N-RAS外显子密码子61上发生点突变2.6)虽然巨噬细胞在小细胞数下对骨髓瘤细胞生长有积极作用，但在大细胞数下也有消极作用。这种负作用是通过巨噬细胞与骨髓瘤细胞之间的白细胞粘附分子相互作用介导的。

Since bone marrow Stromal cells play an important role in the growth of myeloma cells, we used macrophages, a member of stromal cells, as a feeder layer for establishing myeloma cel lines. More than 6 myeloma cell lines have been established. Then, these cell lines were used for the analysis of myeloma cell growth, giving following results.1)Macrophages have positive effect on the growth of myeloma cells and they are useful for establishing myeloma cell lines. 2)Myeloma cells proliferate in response to IL-6 and IL-1. IL-6 secreted by macrophages primarily mediates the stimulatory effect. i 3)With using macrophages as a feeder layer, 6 myeloma cell lines have been established and 4 myeloma cell lines have been maintained in vitro for 3-9 months. 4)Two bone marrow-derived cell lines proliferate absolutely dependently on macrophages or IL-6. However, 4 extramedullary lesion-derived cell lines proliferate spontaneously. 5)Two myeloma cell lines, ILKM3 and KM4, have a point mutation in codon 61 of N-RAS exon 2.6)Although macrophages have positive effect on myeloma cell growth when used at a small cell number, they also have negative effect when used at a higher cell number. Such negative effect is mediated through interaction of leukocyte adhesion molecules between macrophages and myeloma cells.