Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients.
Författare
Summary, in English
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 This elevated CysLT(2)R expression decreased, even below the level of untreated cells, when tamoxifen was withdrawn.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.
Avdelning/ar
- Cellpatologi, Malmö
- Klinisk kemi, Malmö
- Patologi, Malmö
- Kirurgi
- Tumörmikromiljö
- Experimentell patologi, Malmö
- EpiHealth: Epidemiology for Health
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2011
Språk
Engelska
Sidor
9-22
Publikation/Tidskrift/Serie
International Journal of Cancer
Volym
Okt
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
John Wiley & Sons Inc.
Ämne
- Cancer and Oncology
Status
Published
Forskningsgrupp
- Cell Pathology, Malmö
- Clinical Chemistry, Malmö
- Pathology, Malmö
- Surgery
- Experimental Pathology, Malmö
ISBN/ISSN/Övrigt
- ISSN: 0020-7136