Heterogeneous Stromal Signaling within the Tumor Microenvironment Controls the Metastasis of Pancreatic Cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27821486.
- Also identified by DOI 10.1158/0008-5472.CAN-16-1383 and PMC identifier 5245778.
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Abstract
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.
Medical subject headings
- Carcinoma, Pancreatic Ductal
- Gene Expression Regulation, Neoplastic
- Neoplasm Invasiveness
- Pancreatic Neoplasms
- Signal Transduction
- Tumor Microenvironment