Kindler-Röhrborn A, Blass-Kampmann S, Lennartz K, Liepelt U, Minwegen R, Rajewsky M F
Institute of Cell Biology (Cancer Research), University of Essen Medical School, Germany.
Differentiation. 1994 Sep;57(3):215-24. doi: 10.1046/j.1432-0436.1994.5730215.x.
Selective induction of neural tumors in the rat by single-dose exposure of the immature nervous system to ethylnitrosourea (EtNU) is a model for the study of cell lineage-, differentiation stage-, and carcinogen-dependent mechanisms in neuro-oncogenesis. Overall yields and relative frequencies of different types of neural tumors vary with the developmental window chosen for the EtNU-pulse. Precursor cells belonging to different neural lineages and targeted by the carcinogen at distinct developmental stages may thus bear a differential risk of malignant conversion. To specify subpopulations of neural precursors in fetal (prenatal day 18) BDIX-rat brain, four monoclonal antibodies (mAbs) recognizing cell surface differentiation antigens were used: mAb RB13-2 directed against O-acetylated gangliosides and binding to approximately 36% of fetal brain cells (FBC); mAb RB13-6 recognizing a 130 kDa glycoprotein (expressed by approximately 8% of FBC); and mAbs RB21-7 and RB21-15 which bind, respectively, to embryonal neural cell adhesion molecules (N-CAM) and a 24 kDa protein (expressed by approximately 55% and 12% of FBC). Antigen expression profiles were compared with those of 14 primary brain tumors and 16 malignant neural cell lines, all of which had been induced by EtNU on prenatal day 18 in vivo. Monoclonal antibodies RB13-2 and RB21-7 did not bind to any of the tumors or cell lines. In contrast, mAbs RB13-6 and RB21-15 both reacted with 14/14 tumors, and with 16/16 and 10/16 cell lines, respectively. Expression of the latter antigens might thus specify lineage-specific stages of FBC development/differentiation particularly susceptible to EtNU-induced malignant transformation. Two-color fluorescence analyses revealed three subsets of FBC binding mAb RB13-6 (RB13-2+/RB13-6+/RB21-15-; RB13-2-/RB13-6+/RB21-15-; and RB13-2-/RB13-6+/RB21-15+), representing successive stages of differentiation.
通过将未成熟的神经系统单剂量暴露于乙基亚硝基脲（EtNU）来选择性诱导大鼠神经肿瘤，是研究神经肿瘤发生中细胞谱系、分化阶段和致癌物依赖性机制的一种模型。不同类型神经肿瘤的总体发生率和相对频率会因选择用于EtNU脉冲的发育窗口而异。属于不同神经谱系且在不同发育阶段被致癌物靶向的前体细胞，可能因此具有不同的恶性转化风险。为了明确胎儿（产前第18天）BDIX大鼠脑中神经前体细胞亚群，使用了四种识别细胞表面分化抗原的单克隆抗体（mAb）：针对O-乙酰化神经节苷脂且与约36%的胎儿脑细胞（FBC）结合的mAb RB13-2；识别一种130 kDa糖蛋白（约8%的FBC表达）的mAb RB13-6；以及分别与胚胎神经细胞粘附分子（N-CAM）和一种24 kDa蛋白（约55%和12%的FBC表达）结合的mAb RB21-7和RB21-15。将抗原表达谱与14种原发性脑肿瘤和16种恶性神经细胞系的表达谱进行了比较，所有这些都是在产前第18天经体内EtNU诱导产生的。单克隆抗体RB13-2和RB21-7不与任何肿瘤或细胞系结合。相反，mAb RB13-6和RB21-15分别与14/14种肿瘤以及16/16和10/16种细胞系发生反应。因此，后一种抗原的表达可能明确了FBC发育/分化中特别易受EtNU诱导的恶性转化影响的谱系特异性阶段。双色荧光分析揭示了结合mAb RB13-6的FBC的三个亚群（RB13-2+/RB13-6+/RB21-15-；RB13-2-/RB13-6+/RB21-15-；以及RB13-2-/RB13-6+/RB21-15+），代表了连续的分化阶段。
