Cysteinyl leukotriene receptor 1 facilitates tumorigenesis in a mouse model of colitis-associated colon cancer
(2017) In Oncotarget 8(21). p.34773-34786- Abstract
Cysteinyl leukotriene receptor 1 (CysLT1R) 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, CysLT1R disruption was associated with a reduced tumor burden in double-mutant female mice (ApcMin/+/Cysltr1-/-) compared to ApcMin/+ littermates. In the current study, we utilized a genetic approach to investigate the effect of CysLT1R 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... (More)
Cysteinyl leukotriene receptor 1 (CysLT1R) 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, CysLT1R disruption was associated with a reduced tumor burden in double-mutant female mice (ApcMin/+/Cysltr1-/-) compared to ApcMin/+ littermates. In the current study, we utilized a genetic approach to investigate the effect of CysLT1R 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 CysLT1R in colon tumorigenesis.
(Less)
- author
- Osman, Janina LU ; Savari, Sayeh LU ; Chandrashekar, Naveen Kumar ; Bellamkonda, Kishan LU ; Douglas, Desiree LU and Sjölander, Anita LU
- organization
- publishing date
- 2017-05-23
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Journal Article
- in
- Oncotarget
- volume
- 8
- issue
- 21
- pages
- 14 pages
- publisher
- Impact Journals
- external identifiers
-
- pmid:28410235
- scopus:85019888210
- wos:000402051700068
- ISSN
- 1949-2553
- DOI
- 10.18632/oncotarget.16718
- language
- English
- LU publication?
- yes
- id
- d68da3d0-f221-4f80-b481-f026914287b8
- date added to LUP
- 2017-06-09 15:58:49
- date last changed
- 2024-05-26 17:12:53
@article{d68da3d0-f221-4f80-b481-f026914287b8, abstract = {{<p>Cysteinyl leukotriene receptor 1 (CysLT1R) 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, CysLT1R disruption was associated with a reduced tumor burden in double-mutant female mice (ApcMin/+/Cysltr1-/-) compared to ApcMin/+ littermates. In the current study, we utilized a genetic approach to investigate the effect of CysLT1R 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 CysLT1R in colon tumorigenesis.</p>}}, author = {{Osman, Janina and Savari, Sayeh and Chandrashekar, Naveen Kumar and Bellamkonda, Kishan and Douglas, Desiree and Sjölander, Anita}}, issn = {{1949-2553}}, keywords = {{Journal Article}}, language = {{eng}}, month = {{05}}, number = {{21}}, pages = {{34773--34786}}, publisher = {{Impact Journals}}, series = {{Oncotarget}}, title = {{Cysteinyl leukotriene receptor 1 facilitates tumorigenesis in a mouse model of colitis-associated colon cancer}}, url = {{http://dx.doi.org/10.18632/oncotarget.16718}}, doi = {{10.18632/oncotarget.16718}}, volume = {{8}}, year = {{2017}}, }