A low-level expression of human MUC1 mucin enhances lethality of murine tumor cells

We report here the development of a mouse mammary adenocarcinoma cell line containing full-length human MUC1 cDNA that can be more lethal than the par ental cell line. The metastatic murine mammary adenocarcinoma cell line 410 .4 was transfected with cDNA coding for a 42-tandem-repeat version of human MUC1. Two cell lines were selected, one for stable, high expression in vit ro of cell-surface MUC1 (GZHi) and one for stable, low expression in vitro of cell-surface MUC1 (GZLo). Following subcutaneous challenge of CB6F1 mice with various doses of tumor cells, GZHi tumors showed loss of MUC1 express ion; negligible amounts of serum MUC1 mucin were detected and the mice surv ived longer than mice challenged with GZLo or wild-type (410.4) tumor cells . Mice challenged with GZLo tumor cells had shorter survival times than mic e challenged with either GZHi or 410.4 tumor cells. GZLo-challenged mice th at showed rapidly increasing serum MUC1 mucin levels several weeks prior to death had a shorter survival than mice without detectable rising MUC1 seru m levels. Surprisingly, SCID-BEIGE mice challenged with GZLo cells also sur vived for a shorter time than those challenged with either GZHi or 410.4 ce lls. This suggests that MUC1 mucin may also enhance the aggressiveness of G ZLo tumors by non-immune mechanisms.