Shimizu S
Department of Internal Medicine, Kanazawa Medical University.
Nihon Rinsho. 1995 Mar;53(3):557-63.
The mechanism of human multiple myeloma cell growth was studied utilizing twelve myeloma cell lines established in vitro. Seven of them were derived from extramedullary lesions and had the appearance of immature plasmablast. Five were from bone marrow and showed typical plasma cell morphology. Seven extramedullary lesion derived cell lines grew spontaneously and additively proliferated in response to IL-6 and/or gp-130 related cytokines. Three bone marrow derived cell lines grew dependently on a macrophage feeder layer and then on IL-6. Two bone marrow derived cell lines grew in the presence of bone marrow stromal cells or stromal cell culture supernatant, however, they did not proliferate in response to IL-6. While establishing cell lines, it was found that the proliferating fraction was primarily included in a fraction which was non-adherent to stromal cells and was composed of undifferentiated plasmablasts. Undifferentiated plasmablasts proliferated in response to IL-6, while the adherent and mature form of myeloma cells did not proliferate in response to IL-6. Two established bone marrow derived stromal cell dependent myeloma cell lines were adherent to stromal cells, had the mature form of plasma cell morphology and did not proliferate in response to IL-6. These results imply that multiple myeloma cells are composed of heterogenous populations with different maturities and different growth mechanisms.
利用十二种体外建立的骨髓瘤细胞系研究了人多发性骨髓瘤细胞的生长机制。其中七种来源于髓外病变,呈现未成熟浆母细胞的形态。五种来自骨髓,表现出典型的浆细胞形态。七种来源于髓外病变的细胞系能自发生长,并对IL-6和/或gp-130相关细胞因子产生增殖反应。三种来源于骨髓的细胞系依赖巨噬细胞饲养层生长,随后依赖IL-6生长。两种来源于骨髓的细胞系在骨髓基质细胞或基质细胞培养上清液存在的情况下生长,然而,它们对IL-6不产生增殖反应。在建立细胞系的过程中,发现增殖部分主要包含在不粘附于基质细胞的部分中,该部分由未分化的浆母细胞组成。未分化的浆母细胞对IL-6产生增殖反应,而骨髓瘤细胞的粘附和成熟形式对IL-6不产生增殖反应。两种已建立的依赖骨髓基质细胞的骨髓瘤细胞系粘附于基质细胞,具有成熟的浆细胞形态,对IL-6不产生增殖反应。这些结果表明,多发性骨髓瘤细胞由具有不同成熟度和不同生长机制的异质性群体组成。