A low-level expression of human MUC1 mucin enhances lethality of murine tumor cells |
| |
Authors: | Gabrielle L Zimmermann Mark J Krantz Kevin P Kane B Michael Longenecker |
| |
Institution: | (1) Department of Medical Microbiology and Immunology, 141 Medical Sciences, University of Alberta, Edmonton, AB, T6G 2H7, Canada, CA;(2) Biomira Inc., 2011 94 Street, Edmonton, AB, T6N 1H1, Canada e-mail: mlongenecker@biomira.com Tel.: +1-780-450-3761 Fax: +1-780-988-5936, CA |
| |
Abstract: | 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.
Received: 30 November 1999 / Accepted: 13 March 2000 |
| |
Keywords: | MUC1 Animal model Immunotherapy Lethality Tumor aggressiveness |
本文献已被 PubMed SpringerLink 等数据库收录! |
|