Pauwels-Vergely C, Poupon M F
Br J Cancer. 1987 Jul;56(1):7-13. doi: 10.1038/bjc.1987.144.
An increasing number of reports highlight the fact that tumour cells are able to give rise in vitro to immunogenic variants, which are defined in vivo as being non tumorigenic, tum-. We have observed the emergence of immunogenic variants, derived from a primary nickel-induced rat rhabdomyosarcoma established in culture (RMS 9-4/0), resistant to treatment with the chloronitrosourea, chlorozotocin (CZT) (R-lines). They were separated from the whole population of cells by a cloning procedure. Furthermore, we demonstrate that the cloning procedure by itself allows the isolation of tum- variant designated as C-lines. In both cases, the tum- phenotype was observed after s.c. injection of cells into syngeneic rats with a broad range of R9 or C8 cells (10(4) to 10(7). This characteristic was inherited in a stable manner. Athymic mice developed tumours of rat rhabdomyosarcoma origin when grafted with 10(5) cells. Immunization of rats with one R variant (R9) tum- protected the rats grafted with the parental RMS 9-4/0 cells against metastatic invasion of the lungs, but not against local tumour growth, and rats grafted with a CZT-resistant tum+ cell variant S4T (in vivo-derived) against its hepatic and pulmonary metastases, while the local tumour progressed as usual. Immunization of rats with one C variant (C8) tum- cells did not protect them against either metastases or local growth of the implanted tumours. Both R and C lines cells became progressively resistant to NK- and macrophage-induced cytotoxicity. Splenic lymphocyte transfer from immune rats into nude mice, i.e., the Winn test, showed a complete degree of protection against C8 or R9 tumour growth. We conclude that two different antigenicities were revealed, one common to R9 and C8 cells in relation with their selection procedure by repeated cloning. Another antigenicity appeared in the R9 line, selected by CZT-resistance. The anti R9 cell immunization against CZT-resistant tum+ S4T could argue in favour of CZT action in the acquisition of R9 cell antigenicity. More likely, an amplification of antigens rather than induction of a new antigen could explain the protection of anti R9 immunized rats against parental tumour metastases.
越来越多的报告强调肿瘤细胞在体外能够产生免疫原性变体，这些变体在体内被定义为无致瘤性。我们观察到从培养中建立的原发性镍诱导大鼠横纹肌肉瘤（RMS 9-4/0）产生了免疫原性变体，对氯亚硝基脲、氯脲霉素（CZT）治疗具有抗性（R系）。它们通过克隆程序从整个细胞群体中分离出来。此外，我们证明克隆程序本身允许分离出指定为C系的无致瘤性变体。在这两种情况下，将细胞皮下注射到同基因大鼠体内，注射大量R9或C8细胞（10⁴至10⁷）后观察到无致瘤性表型。这种特征以稳定的方式遗传。无胸腺小鼠接种10⁵个细胞后会发生大鼠横纹肌肉瘤起源的肿瘤。用一种R变体（R9）无致瘤性细胞免疫大鼠，可保护接种亲本RMS 9-4/0细胞的大鼠免受肺部转移侵袭，但不能防止局部肿瘤生长，用对CZT耐药的有致瘤性细胞变体S4T（体内衍生）免疫大鼠，可防止其肝转移和肺转移，而局部肿瘤照常进展。用一种C变体（C8）无致瘤性细胞免疫大鼠，不能保护它们免受植入肿瘤的转移或局部生长。R系和C系细胞对NK细胞和巨噬细胞诱导的细胞毒性逐渐产生抗性。将免疫大鼠的脾淋巴细胞转移到裸鼠体内，即温氏试验，显示出对C8或R9肿瘤生长的完全保护程度。我们得出结论，揭示了两种不同的抗原性，一种是R9和C8细胞通过重复克隆的选择程序所共有的。另一种抗原性出现在通过CZT抗性选择的R9系中。针对对CZT耐药的有致瘤性S4T细胞的抗R9细胞免疫可能支持CZT在获得R9细胞抗原性中的作用。更有可能的是，抗原的扩增而非新抗原的诱导可以解释抗R9免疫大鼠对亲本肿瘤转移的保护作用。
