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Heterogeneous Stromal Signaling within the Tumor Microenvironment Controls the Metastasis of Pancreatic Cancer.
Rucki, Agnieszka A; Foley, Kelly; Zhang, Pingbo; Xiao, Qian; Kleponis, Jennifer; Wu, Annie A; Sharma, Rajni; Mo, Guanglan; Liu, Angen; Van Eyk, Jennifer; Jaffee, Elizabeth M; Zheng, Lei.
Afiliación
  • Rucki AA; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Foley K; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Zhang P; Graduate Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Xiao Q; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Kleponis J; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Wu AA; Graduate Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Sharma R; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Mo G; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Liu A; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Van Eyk J; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Jaffee EM; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Zheng L; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Cancer Res ; 77(1): 41-52, 2017 01 01.
Article en En | MEDLINE | ID: mdl-27821486
Understanding how stromal signals regulate the development of pancreatic ductal adenocarcinoma (PDAC) may suggest novel therapeutic interventions in this disease. In this study, we assessed the metastatic role of stromal signals suggested to be important in the PDAC microenvironment. Src and IGF-1R phosphorylated the prometastatic molecule Annexin A2 (AnxA2) at Y23 and Y333 in response to stromal signals HGF and IGF-1, respectively, and IGF-1 expression was regulated by the Sonic Hedgehog (Shh) pathway. Both Shh and HGF were heterogeneously expressed in PDAC stroma, and only dual inhibition of these pathways could significantly suppress AnxA2 phosphorylation, PDAC growth, and metastasis. Taken together, our results illuminate tumor-stromal interactions, which drive metastasis, and provide a mechanism-based rationale for a stroma-directed therapy for PDAC. Cancer Res; 77(1); 41-52. ©2016 AACR.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Carcinoma Ductal Pancreático / Microambiente Tumoral / Invasividad Neoplásica Límite: Animals / Humans Idioma: En Revista: Cancer Res Año: 2017 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 / Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Carcinoma Ductal Pancreático / Microambiente Tumoral / Invasividad Neoplásica Límite: Animals / Humans Idioma: En Revista: Cancer Res Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos