Heterogeneous Stromal Signaling within the Tumor Microenvironment Controls the Metastasis of Pancreatic Cancer

DOI PDF 被引用文献2件
  • Agnieszka A. Rucki
    1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Kelly Foley
    1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Pingbo Zhang
    4Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Qian Xiao
    1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Jennifer Kleponis
    1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Annie A. Wu
    1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Rajni Sharma
    5Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Guanglan Mo
    1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Angen Liu
    1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Jennifer Van Eyk
    7Department of Medicine, Biological Chemistry and Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Elizabeth M. Jaffee
    1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Lei Zheng
    1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

抄録

<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>

収録刊行物

  • Cancer Research

    Cancer Research 77 (1), 41-52, 2017-01-01

    American Association for Cancer Research (AACR)

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