title: MHC imbalance and metastatic spread in Lewis lung carcinoma clones.
abstract: 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.
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000276:immunology*; D002999:Clone Cells; D006183:H-2 Antigens / Q000032:analysis*; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000276:immunology
chemical_list: D006183:H-2 Antigens