| Literature DB >> 24856585 |
Andrew D Rhim1, Paul E Oberstein2, Dafydd H Thomas3, Emily T Mirek4, Carmine F Palermo3, Stephen A Sastra3, Erin N Dekleva4, Tyler Saunders5, Claudia P Becerra6, Ian W Tattersall6, C Benedikt Westphalen7, Jan Kitajewski6, Maite G Fernandez-Barrena8, Martin E Fernandez-Zapico8, Christine Iacobuzio-Donahue5, Kenneth P Olive9, Ben Z Stanger10.
Abstract
Sonic hedgehog (Shh), a soluble ligand overexpressed by neoplastic cells in pancreatic ductal adenocarcinoma (PDAC), drives formation of a fibroblast-rich desmoplastic stroma. To better understand its role in malignant progression, we deleted Shh in a well-defined mouse model of PDAC. As predicted, Shh-deficient tumors had reduced stromal content. Surprisingly, such tumors were more aggressive and exhibited undifferentiated histology, increased vascularity, and heightened proliferation--features that were fully recapitulated in control mice treated with a Smoothened inhibitor. Furthermore, administration of VEGFR blocking antibody selectively improved survival of Shh-deficient tumors, indicating that Hedgehog-driven stroma suppresses tumor growth in part by restraining tumor angiogenesis. Together, these data demonstrate that some components of the tumor stroma can act to restrain tumor growth.Entities:
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Year: 2014 PMID： 24856585 PMCID： PMC4096698 DOI： 10.1016/j.ccr.2014.04.021
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743