The effect of cytokines and adhesion molocules on the apoptosis of the myeloma cell

本研究探讨了多发性骨髓瘤细胞凋亡过程中凋亡相关抗原、粘附受体、细胞因子和癌基因的表达及功能。1）18例新鲜骨髓瘤细胞中有4例表达Fas抗原。BCL-2抗原表达率为95%（19/20）。在任何新鲜骨髓瘤细胞中均未检测到IMN3.1抗原。抗Fas抗体对新鲜细胞无明显诱导凋亡作用。2）多发性骨髓瘤细胞株中，11株细胞株中有6株表达Fas抗原。在这些细胞中，只有一个细胞系ILKM 3在抗Fas抗体处理后显示凋亡。细胞凋亡的研究，利用电子显微镜和DNA分析记录。比较ILKM 3与其他非凋亡倾向细胞的凋亡相关抗原、粘附受体、细胞因子和癌基因的表达，发现凋亡倾向细胞表达Fas和IMN 3. 1抗原，高表达MYC mRNA，低表达BCL-2蛋白。CD 49 d、CD 58、CD 54、CD 56和CD 44在几乎所有细胞和细胞系中表达。CD 49 e、CE 49 f、CD 11 a、SLe-x、LAM-1、CD 41和CD 51以低百分比表达。抗β 1整合素抗体既不完全抑制骨髓基质细胞的粘附，也不诱导显著的细胞凋亡。除β 1-整合素外，其他粘附受体被认为在基质细胞粘附和骨转移中起另一个关键作用。4）新建立的细胞系ILKM 10显示基质细胞依赖性生长。基质细胞依赖性生长不能被IL-6替代。抗β 1整联蛋白抗体治疗不诱导细胞凋亡。ILKM 10似乎是用于分析调节骨髓瘤细胞生长和凋亡的新细胞因子的最佳细胞系。

The expression and function of apoptosis-related antigens, adhesion receptors, cytokines and oncogenes were studied in relation to the apoptotic cell death of multiple myeloma cells.1)Fas antigen was expressed on 4 out of 18 cases of fresh myeloma cells. BCL-2 antigen was expressed in 95%(19/20)of cases. IMN3.1 antigen was not detected in any fresh myeloma cells. Anti-Fas antibody did not significantly induce apoptotic cell death in fresh cells.2)In multiple myeloma cell lines, 6 out of 11 cell lines expressed Fas antigen. Among those only one cell line, ILKM3, showed apoptosis after treatment with anti-Fas antibody. Apoptosis was documented by the studies utilizing electron microscopy and DNA analysis. The comparison of the expression of apoptosis-related antigens, adhesion receptors, cytokines and oncogenes between ILKM3 and other non-apoptosis-prone cells, suggested that apoptosis-prone cells expressed Fas and IMN3.1 antigens, overexpressed MYC mRNA and scaresely expressed BCL-2 protein.3)Fresh myeloma cells and myeloma cell lines almost equally expressed adhesion receptors. CD49d, CD58, CD54, CD56 and CD44 were expressed in almost all the cells and cell lines. CD49e, CE49f, CD11a, SLe-x, LAM-1 CD41 and CD51 were expressed in low percentages. Anti-beta 1 integrin antibodies neither completely inhibited adhesion to bone marrow stromal cells nor induced significant apoptosis. Other adhesion receptors in addition to beta 1-integrin were thought to play another key role in the adherence to stromal cells and apoptosis.4)A newly established cell line, ILKM10, showed stromal cell-dependent growh. Stromal cell-dependent growth was not substituted by IL-6. Treatment by anti-beta 1 integrin antibodies did not induce apoptosis. ILKM10 appears to be the best cell line for the analysis of new cytokines, which regulate the growth and apoptosis in myeloma cells.