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Cancer-Associated Fibroblasts in Pancreatic Cancer Are Reprogrammed by Tumor-Induced Alterations in Genomic DNA Methylation.
Xiao, Qian; Zhou, Donger; Rucki, Agnieszka A; Williams, Jamila; Zhou, Jiaojiao; Mo, Guanglan; Murphy, Adrian; Fujiwara, Kenji; Kleponis, Jennifer; Salman, Bulent; Wolfgang, Christopher L; Anders, Robert A; Zheng, Shu; Jaffee, Elizabeth M; Zheng, Lei.
Afiliación
  • Xiao Q; The Second Affiliated Hospital of the Zhejiang University School of Medicine, Hangzhou, China. Zhejiang University School of Medicine, Hangzhou, China. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University
  • Zhou D; The Second Affiliated Hospital of the Zhejiang University School of Medicine, Hangzhou, China. Zhejiang University School of Medicine, Hangzhou, China. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University
  • Rucki AA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Williams J; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Zhou J; The Second Affiliated Hospital of the Zhejiang University School of Medicine, Hangzhou, China. Zhejiang University School of Medicine, Hangzhou, China. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University
  • Mo G; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care, Johns Hopkins University School of Med
  • Murphy A; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Fujiwara K; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Kleponis J; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Salman B; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Wolfgang CL; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Anders RA; The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Zheng S; Zhejiang University School of Medicine, Hangzhou, China.
  • Jaffee EM; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care, Johns Hopkins University School of Med
  • Zheng L; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care, Johns Hopkins University School of Med
Cancer Res ; 76(18): 5395-404, 2016 09 15.
Article en En | MEDLINE | ID: mdl-27496707
Stromal fibrosis is a prominent histologic characteristic of pancreatic ductal adenocarcinoma (PDAC), but how stromal fibroblasts are regulated in the tumor microenvironment (TME) to support tumor growth is largely unknown. Here we show that PDAC cells can induce DNA methylation in cancer-associated fibroblasts (CAF). Upon direct contact with PDAC cells, DNA methylation of SOCS1 and other genes is induced in mesenchymal stem cells or in CAF that lack SOCS1 methylation at baseline. Silencing or decitabine treatment to block the DNA methylation enzyme DNMT1 inhibited methylation of SOCS1. In contrast, SOCS1 gene methylation and downregulation in CAF activated STAT3 and induced insulin-like growth factor-1 expression to support PDAC cell growth. Moreover, CAF facilitated methylation-dependent growth of PDAC tumor xenografts in mice. The ability of patient-derived CAF with SOCS1 methylation to promote PDAC growth was more robust than CAF without SOCS1 methylation. Overall, our results reveal how PDAC cells can reprogram CAF to modify tumor-stromal interactions in the TME, which promote malignant growth and progression. Cancer Res; 76(18); 5395-404. ©2016 AACR.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Metilación de ADN / Carcinoma Ductal Pancreático / Fibroblastos Asociados al Cáncer / Proteína 1 Supresora de la Señalización de Citocinas Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Cancer Res Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Metilación de ADN / Carcinoma Ductal Pancreático / Fibroblastos Asociados al Cáncer / Proteína 1 Supresora de la Señalización de Citocinas Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Cancer Res Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos