Claas C, Herrmann K, Matzku S, Möller P, Zöller M
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany.
Cell Growth Differ. 1996 May;7(5):663-78.
The specificity of monoclonal antibodies (mABs) obtained after immunization with a metastasizing rat tumor line was evaluated by screening expression in a variety of nonmetastasizing and metastasizing rat tumor lines. mABs, which by immunohistology and Western blotting recognized metastasizing lines, were used to define the physiological expression of the corresponding antigens during ontogeny as well as in adult rats. From a panel of 12 mABs, 2 recognized structures on metastasizing and nonmetastasizing tumor lines, while 10 stained exclusively metastasizing lines. Five of the latter bound to tumor lines metastasizing either hematogenously or via the lymphatic system. All five recognized an epitope on CD44 variant exon v6. The five remaining mABs, recognizing four independent antigenic entities, only stained tumor lines metastasizing via the lymphatics. Surprisingly, these antigens were also detected in normal tissues: three on epithelial cells either widespread or of the upper gastrointestinal tract or the urogenital system, the fourth preferentially on epithelial cells, but also on nerves and hematopoietic precursor cells, and the fifth on many tissues and cells with a predominance of mesenchyme-derived structures. Notably, during ontogeny, expression on these five antigens was induced in different compartments of the developing fetal and/or maternal part of the placenta. The five newly described metastasis-associated antigens share with CD44v the absence of expression on nonmetastasizing tumor lines as well as expression on distinct, nontransformed cells and induction of expression during ontogeny. Thus, tumor progression may rather be initiated by inappropriate expression or up-regulation of genes, which do not display transforming features, than by de novo appearance of "metastasis genes." Accordingly, metastasizing tumor lines may be a valuable tool to identify developmentally regulated gene products.
通过在多种非转移性和转移性大鼠肿瘤细胞系中筛选表达情况，评估了用一种转移性大鼠肿瘤细胞系免疫后获得的单克隆抗体（mABs）的特异性。通过免疫组织化学和蛋白质印迹法识别转移性细胞系的mABs，被用于确定相应抗原在个体发育过程以及成年大鼠中的生理表达。在一组12种mABs中，2种识别转移性和非转移性肿瘤细胞系上的结构，而10种仅对转移性细胞系染色。后者中的5种与通过血行或淋巴系统转移的肿瘤细胞系结合。所有5种都识别CD44可变外显子v6上的一个表位。其余5种mABs识别4个独立的抗原实体，仅对通过淋巴转移的肿瘤细胞系染色。令人惊讶的是，这些抗原在正常组织中也能检测到：3种在上皮细胞上，这些上皮细胞要么广泛分布，要么存在于上消化道或泌尿生殖系统；第4种优先在上皮细胞上，但也存在于神经和造血前体细胞上；第5种存在于许多组织和细胞中，以间充质来源的结构为主。值得注意的是，在个体发育过程中，这5种抗原在发育中的胎盘胎儿和/或母体部分的不同区域被诱导表达。这5种新描述的转移相关抗原与CD44v一样，在非转移性肿瘤细胞系上不表达，在不同的未转化细胞上表达，且在个体发育过程中表达被诱导。因此，肿瘤进展可能更多地是由不具有转化特征的基因的不适当表达或上调引发，而不是由“转移基因”的从头出现引发。相应地，转移性肿瘤细胞系可能是鉴定发育调控基因产物的有价值工具。
