Hochman J, Levy E, Mador N, Gottesman M M, Shearer G M, Okon E
J Cell Biol. 1984 Oct;99(4 Pt 1):1282-8. doi: 10.1083/jcb.99.4.1282.
Mouse lymphoma cells (S49) that grow in suspension culture were selected for increased tumorigenicity through continuous passages in syngeneic BALB/c mice. Developing tumors were classified as high grade malignant lymphoma, small noncleaved type. Variants were selected from these tumorigenic cells that were able to grow as a monolayer attached to their substrate, resembling, in this respect, fibroblastoid cells. Whereas the tumorigenic suspension-growing parental cells were able to induce progressive tumors with an inoculum as low as 100 cells per mouse, the adherent cells were unable to develop as tumors even at an inoculum of 1 X 10(8) cells per mouse. In addition, mice inoculated once with live adherent cells were immunized against 1 X 10(7) suspension-growing cells. Involvement of an immune response in the rejection of tumorigenic S49 cells was suggested by (a) adoptive transfer experiments in which spleen cells from immunized mice protected naive mice and (b) the appearance of antibodies in the sera of immunized syngeneic mice that specifically recognized both adherent and suspension-growing S49 cells and detected differences in [35S]methionine-labeled antigens from these cells. Antibodies raised in rabbits against adherent cells recognized three proteins of 34,000, 61,000, and 72,000 apparent molecular weight in radiolabeled adherent cell extracts that are either absent or present in small amounts in extracts of suspension-growing tumorigenic S49 cells. These findings, taken together with our previous report (Hochman, J., A. Katz, E. Levy, and S. Eshel, 1981, Nature (Lond.), 290:248-249), suggest the S49 system as a novel system for studying growth control in malignant lymphoid cells.
选择在悬浮培养中生长的小鼠淋巴瘤细胞(S49),通过在同基因BALB/c小鼠中连续传代来提高其致瘤性。所形成的肿瘤被分类为高级别恶性淋巴瘤,小无裂细胞型。从这些致瘤细胞中选择出能够作为单层贴附于底物生长的变体,在这方面类似于成纤维样细胞。致瘤性悬浮生长的亲代细胞每只小鼠接种低至100个细胞就能诱导进行性肿瘤,而贴壁细胞即使每只小鼠接种1×10⁸个细胞也无法形成肿瘤。此外,用活的贴壁细胞接种一次的小鼠对1×10⁷个悬浮生长的细胞产生了免疫。(a)免疫小鼠的脾细胞能保护未免疫小鼠的过继转移实验以及(b)免疫同基因小鼠血清中出现特异性识别贴壁和悬浮生长的S49细胞并检测到这些细胞[³⁵S]甲硫氨酸标记抗原差异的抗体,提示免疫反应参与了致瘤性S49细胞的排斥。用兔抗贴壁细胞产生的抗体在放射性标记的贴壁细胞提取物中识别出三种表观分子量分别为34000、61000和72000的蛋白质,这些蛋白质在致瘤性悬浮生长的S49细胞提取物中要么不存在,要么含量很少。这些发现与我们之前的报告(霍克曼,J.,A. 卡茨,E. 利维,和S. 埃舍尔,1981,《自然》(伦敦),290:248 - 249)一起,表明S49系统是研究恶性淋巴细胞生长控制的一个新系统。