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 parental 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 vitro 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 expression; negligible amounts of serum MUC1 mucin were detected and the mice survived longer than mice challenged with GZLo or wild-type (410.4) tumor cells. Mice challenged with GZLo tumor cells had shorter survival times than mice challenged with either GZHi or 410.4 tumor cells. GZLo-challenged mice that showed rapidly increasing serum MUC1 mucin levels several weeks prior to death had a shorter survival than mice without detectable rising MUC1 serum levels. Surprisingly, SCID-BEIGE mice challenged with GZLo cells also survived for a shorter time than those challenged with either GZHi or 410.4 cells. This suggests that MUC1 mucin may also enhance the aggressiveness of GZLo tumors by non-immune mechanisms.
Zimmermann
G L
GL
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
Krantz
M J
MJ
Kane
K P
KP
Longenecker
B M
BM
D000818:Animals; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D018396:Mucin-1 / Q000097:blood / Q000502:physiology*; D009374:Neoplasms, Experimental / Q000401:mortality*
D018396:Mucin-1