Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors.
作者： Lucy Ireland , Almudena Santos , Muhammad S. Ahmed , Carolyn Rainer , Sebastian R. Nielsen
DOI: 10.1158/0008-5472.CAN-16-1201
关键词:
摘要: Tumor associated macrophages (TAM) and myofibroblasts are key drivers in cancer that with drug resistance many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM fibroblasts contribute to chemoresistance is unclear. In this study, we found directly support cells secreting insulin-like growth factors 1 2 (IGF), activate Insulin/IGF receptors on cells. Immunohistochemical analysis biopsies from patients revealed 72% expressed activated insulin/IGF tumor cells, positively correlates increased CD163+ infiltration. vivo, were main sources IGF production, pharmacological blockade sensitized tumors gemcitabine. These findings suggest inhibition combination chemotherapy could benefit PDAC patients, insulin/IGF1R activation may be used as a biomarker identify for such therapeutic intervention.
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