Cysteinyl leukotriene receptor 1 facilitates tumorigenesis in a mouse model of colitis-associated colon cancer
| Autor: | Sayeh Savari, Kishan Bellamkonda, Janina Osman, Naveen Kumar Chandrashekar, Desiree Douglas, Anita Sjölander |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Colorectal cancer CysLT1 receptor Azoxymethane Mucin 2 medicine.disease_cause digestive system Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine otorhinolaryngologic diseases Animals Colitis Receptor beta Catenin Receptors Leukotriene business.industry Body Weight Dextran Sulfate medicine.disease digestive system diseases LTD4 signaling Cysteinyl leukotriene receptor 1 Disease Models Animal 030104 developmental biology colitis-associated colon cancer (CAC) Oncology chemistry colon cancer inflammation Cyclooxygenase 2 030220 oncology & carcinogenesis Colonic Neoplasms Cancer research Carcinogenesis business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Janina Osman 1, * , Sayeh Savari 1, * , Naveen Kumar Chandrashekar 1 , Kishan Bellamkonda 1 , Desiree Douglas 1 , Anita Sjolander 1 1 Division of Cell and Experimental Pathology, Department of Translational Medicine, Lund University, Skane University Hospital, SE-205 02, Malmo, Sweden * These authors contributed equally to this work Correspondence to: Anita Sjolander, email: Anita.Sjolander@med.lu.se Keywords: CysLT 1 receptor, LTD 4 signaling, colon cancer, colitis-associated colon cancer (CAC), inflammation Received: December 19, 2016 Accepted: March 20, 2017 Published: March 30, 2017 ABSTRACT Cysteinyl leukotriene receptor 1 (CysLT 1 R) has been shown to be up-regulated in the adenocarcinomas of colorectal cancer patients, which is associated with a poor prognosis. In a spontaneous model of colon cancer, CysLT 1 R disruption was associated with a reduced tumor burden in double-mutant female mice ( Apc Min/+/ Cysltr1 −/− ) compared to Apc Min/+ littermates. In the current study, we utilized a genetic approach to investigate the effect of CysLT 1 R in the induced azoxymethane/dextran sulfate sodium (AOM/DSS) model of colitis-associated colon cancer. We found that AOM/DSS female mice with a global disruption of the Cysltr1 gene (Cysltr1 −/− ) had a higher relative body weight, a more normal weight/length colon ratio and smaller-sized colonic polyps compared to AOM/DSS wild-type counterparts. The Cysltr1 −/− colonic polyps exhibited low-grade dysplasia, while wild-type polyps had an adenoma-like phenotype. The Cysltr1 −/− colonic polyps exhibited significant decreases in nuclear β-catenin and COX-2 protein expression, while the normal crypts surrounding the polyps exhibited increased Mucin 2 expression. Furthermore, Cysltr1 −/− mice exhibited an overall reduction in inflammation, with a significant decrease in proinflammatory cytokines, polyp 5-LOX expression and infiltration of CD45 leukocytes and F4/80 macrophages. In conclusion, the present genetic approach in an AOM/DSS model further supports an important role for CysLT 1 R in colon tumorigenesis. |
| Databáze: | OpenAIRE |
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