Heterogeneous Stromal Signaling within the Tumor Microenvironment Controls the Metastasis of Pancreatic Cancer
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- Agnieszka A. Rucki
- 1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- Kelly Foley
- 1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- Pingbo Zhang
- 4Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- Qian Xiao
- 1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- Jennifer Kleponis
- 1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- Annie A. Wu
- 1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- Rajni Sharma
- 5Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- Guanglan Mo
- 1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- Angen Liu
- 1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- Jennifer Van Eyk
- 7Department of Medicine, Biological Chemistry and Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- Elizabeth M. Jaffee
- 1The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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- 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
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- Cancer Research
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Cancer Research 77 (1), 41-52, 2017-01-01
American Association for Cancer Research (AACR)