We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The immune response to sporadic colorectal cancer in a novel mouse model.
- Authors
Czéh, M; Loddenkemper, C; Shalapour, S; Schön, C; Robine, S; Goldscheid, E; Stein, H; Schüler, T; Willimsky, G; Blankenstein, T
- Abstract
Current mouse models do not reflect the sporadic nature of colon cancer and do not allow the analysis of antitumor immune response because of the lack of known tumor-specific antigens. Two transgenic mouse models with spontaneous tumor development were generated, directing the expression of SV40T antigen (Tag) either constitutively (Vil-Cre × LoxP-Tag-transgenic mice) or stochastically (Vil-Cre-ERT2 × LoxP-Tag-transgenic mice) into the putative stem cell region of the crypt of Lieberkühn. Tumor development and antitumor immune response were monitored. Vil-Cre × LoxP-Tag mice developed multiple adenocarcinomas of the small intestine and colon at an average age of 6 months. During the tumor development, Tag-specific immunoglobulin G (IgG) antibodies were induced in half of the mice, although they had developed neonatal cytotoxic T lymphocyte (CTL) tolerance. This model shows similarity to hereditary colon cancer but not to the sporadic tumor development. Therefore, the conditional Vil-Cre-ERT2 × LoxP-Tag mice were established, in which expression of the dormant Tag was induced by stochastic, tissue-specific activation of Cre recombinase. These mice spontaneously developed highly invasive, metastasizing colon carcinomas at an average age of 20 months. Colon carcinomas expressed epithelial and/or neuroendocrine markers depending on the grade of differentiation. Young Vil-Cre-ERT2 × LoxP-Tag mice had retained CTL responses against epitope IV of Tag. The tumors induced strong anti-Tag IgG responses. We report, for the first time, a mouse model based on stochastic, tissue-specific activation of a dormant oncogene in the colon allowing the analysis of antitumor immune response against primary colorectal cancer.
- Subjects
IMMUNE response; COLON cancer; LABORATORY mice; EPITOPES; T cells; ANTINEOPLASTIC agents; GENE expression
- Publication
Oncogene, 2010, Vol 29, Issue 50, p6591
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2010.388