Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients.
(2011) In International Journal of Cancer Okt. p.9-22- Abstract
- The fact that breast cancer patients with local or distal dissemination exhibit decreased survival, promotes a search for novel mechanisms to suppress such tumor progression. Here we have determined the expression of pro-inflammatory cysteinyl leukotriene receptors (CysLTRs) in breast tumor tissue and their signaling effect on breast cancer cell functions related to tumor progression. Patients with breast tumors characterized by high CysLT(1)R and low CysLT(2)R expression levels exhibited increased risk of cancer-induced death in univariate analysis for both the total patient group (HR = 2.88, 95% CI 1.11-7.41), as well as patients with large (>20mm) tumors (HR = 5.08, 95% CI 1.39-18.5). Multivariate analysis revealed that patients with... (More)
- The fact that breast cancer patients with local or distal dissemination exhibit decreased survival, promotes a search for novel mechanisms to suppress such tumor progression. Here we have determined the expression of pro-inflammatory cysteinyl leukotriene receptors (CysLTRs) in breast tumor tissue and their signaling effect on breast cancer cell functions related to tumor progression. Patients with breast tumors characterized by high CysLT(1)R and low CysLT(2)R expression levels exhibited increased risk of cancer-induced death in univariate analysis for both the total patient group (HR = 2.88, 95% CI 1.11-7.41), as well as patients with large (>20mm) tumors (HR = 5.08, 95% CI 1.39-18.5). Multivariate analysis revealed that patients with large tumors exhibiting high CysLT(1)R and low CysLT(2)R expression levels had a significantly reduced survival, also when adjusted for established prognostic parameters (HR = 7.51, 95% CI 1.83-30.8). In patients with large (>20mm) tumors, elevated CysLT(2)R expression predicted an improved five-year survival (log-rank test P = 0.04). Surprisingly, for longer time periods this prognostic value was lost. This disappearance coincided with the termination of hormonal treatment. Tamoxifen preserved and even induced transcription of CysLT(2)R, but not CysLT(1)R, in ER-positive MCF-7 breast cancer cells. This elevated CysLT(2)R expression decreased, even below the level of untreated cells, when tamoxifen was withdrawn. CysLT(2)R signaling reduced MCF-7 cell migration, but had no effect on either proliferation or apoptosis. Our data indicate that low CysLT(1)R together with high CysLT(2)R expression levels might be useful parameters in prognostication and treatment stratification of breast cancer patients. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1688428
- author
- Magnusson, Cecilia LU ; Liu, Jian LU ; Ehrnström, Roy LU ; Manjer, Jonas LU ; Jirström, Karin LU ; Andersson, Tommy LU and Sjölander, Anita LU
- organization
-
- Cell Pathology, Malmö (research group)
- Clinical Chemistry, Malmö (research group)
- Pathology, Malmö (research group)
- Surgery (research group)
- Tumor microenvironment
- Experimental Pathology, Malmö (research group)
- EpiHealth: Epidemiology for Health
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- International Journal of Cancer
- volume
- Okt
- pages
- 9 - 22
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000289987300002
- pmid:20824707
- scopus:79955420164
- ISSN
- 0020-7136
- DOI
- 10.1002/ijc.25648
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Pathology (013031100), Surgery Research Unit (013242220), Pathology (Malmö) (013031000), Cell Pathology (013031400), Clinical Chemistry, Malmö (013016000), Pathology, (Lund) (013030000)
- id
- 515b179d-1490-407a-b31a-15f3066cec85 (old id 1688428)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20824707?dopt=Abstract
- date added to LUP
- 2016-04-04 08:06:36
- date last changed
- 2024-01-29 02:54:21
@article{515b179d-1490-407a-b31a-15f3066cec85, abstract = {{The fact that breast cancer patients with local or distal dissemination exhibit decreased survival, promotes a search for novel mechanisms to suppress such tumor progression. Here we have determined the expression of pro-inflammatory cysteinyl leukotriene receptors (CysLTRs) in breast tumor tissue and their signaling effect on breast cancer cell functions related to tumor progression. Patients with breast tumors characterized by high CysLT(1)R and low CysLT(2)R expression levels exhibited increased risk of cancer-induced death in univariate analysis for both the total patient group (HR = 2.88, 95% CI 1.11-7.41), as well as patients with large (>20mm) tumors (HR = 5.08, 95% CI 1.39-18.5). Multivariate analysis revealed that patients with large tumors exhibiting high CysLT(1)R and low CysLT(2)R expression levels had a significantly reduced survival, also when adjusted for established prognostic parameters (HR = 7.51, 95% CI 1.83-30.8). In patients with large (>20mm) tumors, elevated CysLT(2)R expression predicted an improved five-year survival (log-rank test P = 0.04). Surprisingly, for longer time periods this prognostic value was lost. This disappearance coincided with the termination of hormonal treatment. Tamoxifen preserved and even induced transcription of CysLT(2)R, but not CysLT(1)R, in ER-positive MCF-7 breast cancer cells. This elevated CysLT(2)R expression decreased, even below the level of untreated cells, when tamoxifen was withdrawn. CysLT(2)R signaling reduced MCF-7 cell migration, but had no effect on either proliferation or apoptosis. Our data indicate that low CysLT(1)R together with high CysLT(2)R expression levels might be useful parameters in prognostication and treatment stratification of breast cancer patients.}}, author = {{Magnusson, Cecilia and Liu, Jian and Ehrnström, Roy and Manjer, Jonas and Jirström, Karin and Andersson, Tommy and Sjölander, Anita}}, issn = {{0020-7136}}, language = {{eng}}, pages = {{9--22}}, publisher = {{John Wiley & Sons Inc.}}, series = {{International Journal of Cancer}}, title = {{Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients.}}, url = {{http://dx.doi.org/10.1002/ijc.25648}}, doi = {{10.1002/ijc.25648}}, volume = {{Okt}}, year = {{2011}}, }