Eisenbach L, Segal S, Feldman M
Int J Cancer. 1983 Jul 15;32(1):113-20. doi: 10.1002/ijc.2910320118.
Imbalance in the Kb and Db region encoded molecules is observed in Lewis lung carcinoma clones. The uncloned metastatic population and the D122 high-metastatic clone show no expression of H-2Kb products, while the nonmetastatic A9 clone expresses Kb products. Twenty-nine new subclones of 3LL and A9 were analyzed for D-end and K-end membrane expression, primary growth rate and metastatic spread. We show that the imbalance in H-2Kb to H-2Db is correlated with metastatic properties of a given clone, but local tumor growth is not. A "low Kb/low Db" phenotype is nonmetastatic as is a "high Kb/high Db" phenotype; a "low Kb/high Db" is highly metastatic and a "medium Kb/high Db" is moderately metastatic. We find support for this notion of imbalance in experiments on MHC modulation by interferon and retinoic acid. Interferon increases both Kb and Db expression of A9 and D122 clones yet the net increase of Db was greater than Kb. This was associated with an increase in metastasis formation. Retinoic acid increases the expression of the Db gene product on the nonmetastatic A9, clone, without apparent changes in Kb expression. This treatment shifts the A9 to a high-metastatic phenotype. The significance of this imbalance to the tumor--host relationship is discussed.
在Lewis肺癌克隆中观察到Kb和Db区域编码分子的失衡。未克隆的转移群体和D122高转移克隆未显示H-2Kb产物的表达，而非转移的A9克隆表达Kb产物。对3LL和A9的29个新亚克隆进行了D端和K端膜表达、原发生长率和转移扩散分析。我们发现，H-2Kb与H-2Db的失衡与特定克隆的转移特性相关，但与局部肿瘤生长无关。“低Kb/低Db”表型是非转移的，“高Kb/高Db”表型也是如此；“低Kb/高Db”是高转移的，“中Kb/高Db”是中度转移的。我们在干扰素和视黄酸对MHC调节的实验中找到了对这种失衡概念的支持。干扰素增加了A9和D122克隆的Kb和Db表达，但Db的净增加大于Kb。这与转移形成的增加有关。视黄酸增加了非转移A9克隆上Db基因产物的表达，而Kb表达没有明显变化。这种处理使A9转变为高转移表型。讨论了这种失衡对肿瘤-宿主关系的意义。
