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.

Overexpression of a set of genes, including WISP-1, common to pulmonary metastases of both mouse D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines

“…The highly metastatic D122 clone of the C57BL/6-derived Lewis lung carcinoma (Eisenbach et al, 1983) was maintained in DMEM supplemented with 10% heat-inactivated fetal calf serum, glutamine, combined antibiotics, sodium pyruvate and nonessential amino acids. The highly metastatic B16-F10.9 clone of the C57BL/ 6-derived malignant melanoma (Porgador et al, 1989) was grown in DMEM supplemented with 10% heat-inactivated fetal calf serum, glutamine and combined antibiotics.…”

Loss of monomorphic and polymorphic HLA antigens in metastatic breast and colon carcinoma

“…Four (Benacerraf, 1981;Linsk & Goodenow, 1986;Schwartz, 1982). The class I MHC molecule consists of three alpha regimes, covalently linked to beta-2-microglobulin (beta 2m), which are encoded by separate genes, and linked prior to expression at the cell membrane (Ploegh et al, 1981;Arce-Gomez, 1978 (Eisenbach et al, 1983;1985). Studies on the expression of human MHC class I antigens in primary vs metastatic tumour are limited; for example malignant melanoma, digestive tract, and laryngeal tumours (Ruiz-Cabello et al, 1989;Esteban et al, 1989).…”

“…With these immunogenic tumours, those with a high level of MHC antigen expression show low metastatic ability; transfection and subsequent expression of the H2K gene into otherwise highly metastatic H2K-negative tumour cell variants reduces tumour growth, and prevents metastasis (Eisenbach et al, 1983;1985). Studies on the expression of human MHC class I antigens in primary vs metastatic tumour are limited; for example malignant melanoma, digestive tract, and laryngeal tumours (Ruiz-Cabello et al, 1989;Esteban et al, 1989).…”

Modification of PDGFα receptor expression or function alters the metastatic phenotype of 3LL cells

“…In the 3LL system, we have also reported that reduced expression of MHC class I antigens on the cell surface correlates with reduced immunogenicity and increased malignancy of tumor clones (Eisenbach et al, 1983). The low metastatic clone A9, however, does express signi®cant levels of MHC class I molecules and is highly immunogenic, i.e.…”

“…We have isolated, by limiting dilution, high-and lowmetastatic clones from the parental 3LL murine tumor; the high-metastatic clones metastasize exclusively to the lungs (DeBaetselier et al, 1980;Eisenbach et al, 1983). An earlier report of ours showed that the PDGFa receptor is preferentially expressed in high-metastatic but not in low-metastatic 3LL clones (Do et al, 1992).…”