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Loss of androgen receptor signaling in prostate cancer-associated fibroblasts (CAFs) promotes CCL2- and CXCL8-mediated cancer cell migration.
Cioni, Bianca; Nevedomskaya, Ekaterina; Melis, Monique H M; van Burgsteden, Johan; Stelloo, Suzan; Hodel, Emma; Spinozzi, Daniele; de Jong, Jeroen; van der Poel, Henk; de Boer, Jan Paul; Wessels, Lodewyk F A; Zwart, Wilbert; Bergman, Andries M.
Afiliação
  • Cioni B; Division of Oncogenomics, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • Nevedomskaya E; Division of Oncogenomics, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • Melis MHM; Division of Molecular Carcinogenesis, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • van Burgsteden J; Oncode Institute, The Netherlands.
  • Stelloo S; Division of Molecular Genetics, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • Hodel E; Division of Molecular Genetics, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • Spinozzi D; Division of Oncogenomics, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • de Jong J; Faculty of EEMCS, Delft University of Technology, Delft, The Netherlands.
  • van der Poel H; Division of Molecular Genetics, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • de Boer JP; Division of Molecular Genetics, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • Wessels LFA; Division of Pathology, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • Zwart W; Division of Urology, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • Bergman AM; Division of Oncogenomics, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
Mol Oncol ; 12(8): 1308-1323, 2018 08.
Article em En | MEDLINE | ID: mdl-29808619
Fibroblasts are abundantly present in the prostate tumor microenvironment (TME), including cancer-associated fibroblasts (CAFs) which play a key role in cancer development. Androgen receptor (AR) signaling is the main driver of prostate cancer (PCa) progression, and stromal cells in the TME also express AR. High-grade tumor and poor clinical outcome are associated with low AR expression in the TME, which suggests a protective role of AR signaling in the stroma against PCa development. However, the mechanism of this relation is not clear. In this study, we isolated AR-expressing CAF-like cells. Testosterone (R1881) exposure did not affect CAF-like cell morphology, proliferation, or motility. PCa cell growth was not affected by culturing in medium from R1881-exposed CAF-like cells; however, migration of PCa cells was inhibited. AR chromatin immune precipitation sequencing (ChIP-seq) was performed and motif search suggested that AR in CAF-like cells bound the chromatin through AP-1-elements upon R1881 exposure, inducing enhancer-mediated AR chromatin interactions. The vast majority of chromatin binding sites in CAF-like cells were unique and not shared with AR sites observed in PCa cell lines or tumors. AR signaling in CAF-like cells decreased expression of multiple cytokines; most notably CCL2 and CXCL8 and both cytokines increased migration of PCa cells. These results suggest direct paracrine regulation of PCa cell migration by CAFs through AR signaling.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Transdução de Sinais / Receptores Androgênicos / Movimento Celular / Interleucina-8 / Quimiocina CCL2 / Fibroblastos Associados a Câncer Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Transdução de Sinais / Receptores Androgênicos / Movimento Celular / Interleucina-8 / Quimiocina CCL2 / Fibroblastos Associados a Câncer Idioma: En Ano de publicação: 2018 Tipo de documento: Article