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Recruited T cells promote the bladder cancer metastasis via up-regulation of the estrogen receptor β/IL-1/c-MET signals
- Source :
- Cancer letters. 430
- Publication Year :
- 2017
-
Abstract
- Clinical data indicates that T cells can be recruited to bladder cancer (BCa), yet the impact of T cells on BCa progression remains unclear. In the present study, we found that T cells were recruited more to BCa tissues than to the surrounding normal bladder tissues. Results from an in vitro co-culture system also found that BCa recruited more CD4+ T cells than did normal bladder cells. The recruiting of T cells to BCa tissues may increase the proliferation and invasion of BCa cells. Mechanistic studies revealed that infiltrating T cells stimulate BCa estrogen receptor beta (ERβ) signaling and consequently increase the expression of MET proto-oncogene, receptor tyrosine kinase (c-MET), through either direct binding to its promoter or via modulation of IL-1 expression. Interruption of ERβ/c-MET or ERβ/IL-1/c-MET signaling via ERβ-shRNA, IL-1 antagonist, or the c-MET inhibitor, SU11274, could partially reverse the T cell-enhanced BCa cell invasion and proliferation. Finally, the mouse BCa model with xenografted BCa 5637 cells with T (HH) cells confirmed the results of in vitro co-culture studies showing that infiltrating T cells could promote BCa metastasis via modulation of the ERβ/c-MET or ERβ/IL-1/c-MET signaling pathways. These findings may provide a new therapeutic approach to better combat BCa progression via targeting these newly identified signaling pathways.
- Subjects :
- 0301 basic medicine
CD4-Positive T-Lymphocytes
Male
Cancer Research
Indoles
Estrogen receptor
Proto-Oncogene Mas
Receptor tyrosine kinase
Piperazines
Metastasis
chemistry.chemical_compound
Mice
0302 clinical medicine
Cell Movement
skin and connective tissue diseases
Promoter Regions, Genetic
Sulfonamides
biology
Chemistry
Proto-Oncogene Proteins c-met
Up-Regulation
Gene Expression Regulation, Neoplastic
Oncology
030220 oncology & carcinogenesis
Disease Progression
Female
Signal transduction
Signal Transduction
C-Met
Urinary Bladder
Mice, Nude
Cystectomy
03 medical and health sciences
Downregulation and upregulation
Cell Line, Tumor
medicine
Animals
Estrogen Receptor beta
Humans
Neoplasm Invasiveness
Estrogen receptor beta
Cell Proliferation
Bladder cancer
medicine.disease
Xenograft Model Antitumor Assays
030104 developmental biology
Pyrimidines
Urinary Bladder Neoplasms
biology.protein
Cancer research
Pyrazoles
Interleukin-1
Subjects
Details
- ISSN :
- 18727980
- Volume :
- 430
- Database :
- OpenAIRE
- Journal :
- Cancer letters
- Accession number :
- edsair.doi.dedup.....06a1f4df35f9e0e44e48c62add67b860