Association between expression of a tumor-associated carbohydrate epitope and the proliferative and tumorigenic activity of a human squamous lung cancer cell line and epitope-positive and -negative sublines.

A previously described epitope (designated 43-9F) with high specificity for human squamous carcinoma and adenocarcinoma of the lung is here reported to be associated with the proliferative and tumorigenic activity of a cloned human squamous lung carcinoma (SLC) cell line (SLC-L11) and a number of cloned sublines. Lines with appreciable 43-9F epitope density (43-9F+) had a short population doubling time and were tumorigenic in athymic nude mice, whereas clones with low 43-9F epitope density (43-9F-) of the same line had longer population doubling times and did not result in 43-9F- tumors in athymic nude mice. Some of the 43-9F- clones reverted to the 43-9F+ phenotype and then became tumorigenic. Two other SLC lines (SLC-L12 and SLC-L13), positive and negative, respectively, for 43-9F also expressed tumorigenic and proliferative behavior concordant with the data for SLC-L11 and its sublines. Cell lines of human squamous cell carcinomas had a pronounced intratumoral heterogeneity in respect to 43-9F epitope expression. Fluorescence-activated cell sorting of cells with high and low 43-9F density and subsequent cloning demonstrated that the cloning capacity was confined almost exclusively to cells with high antigen density. Immunoaffinity chromatography and gel filtration showed that the epitope was expressed in glycoproteins with molecular weights in the range of 5 X 10(6)-5 X 10(4). Mild alkaline hydrolysis reduced the binding of 43-9F antibody to SLC-glycoproteins while neuraminidase treatment augmented the 43-9F antibody binding. It is concluded that expression of 43-9F+ glycoproteins seems linked to the proliferative and tumorigenic features of human squamous lung carcinoma cell lines.