Martin, Maria and Kesselring, Rebecca K. and Saidou, Balam and Brunner, Stefan M. and Schiechl, Gabriela and Mouris, Verena F. and Wege, Anja K. and Ruemmele, Petra and Schlitt, Hans J. and Geissler, Edward K. and Fichtner-Feigl, Stefan (2015) RORt(+) hematopoietic cells are necessary for tumor cell proliferation during colitis-associated tumorigenesis in mice. EUROPEAN JOURNAL OF IMMUNOLOGY, 45 (6). pp. 1667-1679. ISSN 0014-2980, 1521-4141
Full text not available from this repository. (Request a copy)Abstract
Colorectal cancer (CRC) is one of the most common tumor entities. In patients with inflammatory bowel diseases, the development of colitis-associated colon cancer is considered a dangerous long-term complication. IL-17A and the transcription factor retinoic acid receptor-related orphan receptor t (RORt) play fundamental roles in the pathogenesis of inflammatory bowel diseases; in human studies, we detected a dense infiltration of RORt-dependent CD4(+)IL17A(+) T helper (Th)17 cells in specimens of CRC, ulcerative colitis, and ulcerative colitis-associated colorectal cancer. However, the mechanistic role of RORt(+) hematopoietic cells in colitis-associated tumorigenesis remains unclear. To investigate colitis-associated colon tumorigenesis, we conducted studies in the AOM+DSS mouse model that revealed the importance of RORt for colon tumor progression. In the absence of RORt-dependent Th17 lymphocytes, mice showed signs of intense chronic colitis, but developed significantly fewer macroscopic tumor nodules. The reduction of tumor development in RORt(-/-) mice was not due to reduced colon tumor initiation. However, the proliferation rate of tumor cells was reduced in the absence of RORt-dependent Th17 cells and tumor cells showed pronounced signs of senescence-associated epigenetic and lysosomal changes. These results indicate an important role for the immunological milieu in colitis-associated cancer, which is shaped in-part by RORt-dependent Th17 lymphocytes that support CRC growth.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ROR-GAMMA-T; COLORECTAL-CANCER; TH17 CELLS; ULCERATIVE-COLITIS; CUTTING EDGE; TNF-ALPHA; INFLAMMATION; IL-17; INTERLEUKIN-17; DIFFERENTIATION; AOM plus DSS; Colitis-associated colorectal cancer; Th17 cells; IL-17; RORt |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Pathologie Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2019 07:34 |
| Last Modified: | 15 Jul 2019 07:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5422 |
Actions (login required)
 |
View Item |
