MHC imbalance and metastatic spread in Lewis lung carcinoma clones

Imbalance in the K^b and D^b 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-2K^b products, while the non-metastatic A9 clone expresses K^b 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-2K^b to H-2D^b is correlated with metastatic properties of a given clone, but local tumor growth is not. A “low K^b/low D⁹” phenotype is nonmetastatic as is a “high K^b/high D^b” phenotype; a “low K^b/high D^b” is highly metastatic and a “medium K^b/high D^b” is moderately metastatic. We find support for this notion of imbalance in experiments on MHC modulation by interferon and retinoic acid. Interferon increases both K^b and D^b expression of A9 and D122 clones yet the net increase of D^b was greater than K^b. This was associated with an increase in metastasis formation. Retinoic acid increases the expression of the D^b gene product on the nonmetastatic A9, clone, without apparent changes in K^b expression. This treatment shifts the A9 to a high-metastatic phenotype. The significance of this imbalance to the tumor — host relationship is discussed.