Tumor progression in metastasis: an experimental approach using lectin resistant tumor variants.
Tumor progression in metastasis: an experimental approach using lectin resistant tumor variants.
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转移中的肿瘤进展：使用凝集素抗性肿瘤变体的实验方法。
DOI：
10.1007/bf00048223
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Frost,P
中科院分区：
文献类型：
--
作者：
Kerbel,RS;Dennis,JW;Largarde,AE;Frost,P
描述了一种转移性癌症肿瘤进展的新模型，该模型源于从高度转移性小鼠肿瘤 MDAY-D2 中衍生出稳定的非转移性变异的尝试。这些变体是通过在诱变后使用有毒浓度的麦芽凝集素（WGA）作为选择剂选择所谓的凝集素抗性（LecR）膜突变体而获得的。克隆的 WGAR 变体几乎都具有高度致瘤性和转移性，但显示出改变的生长特性，这高度暗示在转移之前发生的主要细胞表型改变。自发性内脏转移始终由 WGA 敏感（WGAS）“回复”肿瘤细胞组成的发现证实了这一点。这种回复体也在皮下接种部位出现，并且随着时间的推移，该部位的肿瘤细胞比例不断增加。 WGAS/高转移表型在体外或体内均稳定，这意味着WGAR→WGAS转变具有潜在的遗传基础。因此，由于内在的细胞缺陷或宿主施加的屏障，WGAR肿瘤细胞似乎无法转移，但是可以通过WGAR肿瘤细胞中的遗传改变来规避这种阻碍，这种改变伴随着WGAR表型的逆转。还获得了非致瘤（tum-）WGAR变体，但在这些情况下，诱变处理本身似乎负责tum表型的发展。致瘤性的降低具有潜在的免疫学基础，这一发现可用于免疫治疗性治疗低免疫原性肿瘤的内脏转移。在这些研究中，重点放在使用具有各种稳定耐药遗传标记的肿瘤细胞群来监测肿瘤发生、肿瘤进展和转移方面的巨大潜力。
A novel model of tumor progression in metastatic cancer is described which grew out of attempts to derive stable non-metastatic variants from a highly metastatic mouse tumor called MDAY-D2. The variants were obtained by selection of so-called lectin-resistant (LecR) membrane mutants using toxic concentrations of wheat germ agglutinin (WGA) as the selective agent, after mutagenesis. Cloned WGARvariants almost all appeared to be highly tumorigenic and metastatic, but displayed altered growth properties which were highly suggestive of major cellular phenotypic alterations occurring prior to metastasis. This were confirmed with the discovery that spontaneous visceral metastases always consisted of WGA-sensitive (WGAS) ‘revertant’ tumor cells. Such revertants also arose at the site of the subcutaneous inoculation and, with time, comprised an increasing proportion of the tumor cells at that location. The WGAS/high metastatic phenotype was stable in vitro or in vivo, implying the WGAR→WGASshift had an underlying genetic basis. Thus, it appeared that the WGARtumor cells could not metastasize, because of either an intrinsic cellular defect or a host imposed barrier, but that this block could be circumvented through a genetic change in the WGARtumor cells which was accompanied by reversion of the WGARphenotype.Non-tumorigenic (tum-) WGARvariants were also obtained, but in these cases the mutagenesis treatment itself appeared responsible for development of the tum-phenotype. The reduced tumorigenicity had an underlying immunological basis, a finding which could be exploited to immunotherapeutically treat established visceral metastases of poorly immunogenic tumors.Throughout these studies, emphasis was placed on the considerable potential of using tumor cell populations having various stable drug-resistant genetic markers to monitor aspects of tumorigenesis, tumor progression, and metastasis.