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Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma.
Rhim, Andrew D; Oberstein, Paul E; Thomas, Dafydd H; Mirek, Emily T; Palermo, Carmine F; Sastra, Stephen A; Dekleva, Erin N; Saunders, Tyler; Becerra, Claudia P; Tattersall, Ian W; Westphalen, C Benedikt; Kitajewski, Jan; Fernandez-Barrena, Maite G; Fernandez-Zapico, Martin E; Iacobuzio-Donahue, Christine; Olive, Kenneth P; Stanger, Ben Z.
Affiliation
  • Rhim AD; Division of Gastroenterology, Department of Internal Medicine and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Gastroenterology Division, Department of Medicine and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of
  • Oberstein PE; Division of Hematology and Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  • Thomas DH; Division of Digestive and Liver Diseases in the Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, N
  • Mirek ET; Gastroenterology Division, Department of Medicine and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Palermo CF; Division of Digestive and Liver Diseases in the Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, N
  • Sastra SA; Division of Digestive and Liver Diseases in the Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, N
  • Dekleva EN; Gastroenterology Division, Department of Medicine and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Saunders T; Sol Goldman Pancreatic Cancer Research Center and Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Becerra CP; Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  • Tattersall IW; Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  • Westphalen CB; Division of Digestive and Liver Diseases in the Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  • Kitajewski J; Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  • Fernandez-Barrena MG; Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
  • Fernandez-Zapico ME; Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
  • Iacobuzio-Donahue C; Sol Goldman Pancreatic Cancer Research Center and Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Olive KP; Division of Digestive and Liver Diseases in the Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, N
  • Stanger BZ; Gastroenterology Division, Department of Medicine and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bstanger@exchange.upenn.edu.
Cancer Cell ; 25(6): 735-47, 2014 Jun 16.
Article in En | MEDLINE | ID: mdl-24856585
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Stromal Cells / Carcinoma, Pancreatic Ductal Type of study: Clinical_trials / Prognostic_studies Limits: Animals / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2014 Type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Stromal Cells / Carcinoma, Pancreatic Ductal Type of study: Clinical_trials / Prognostic_studies Limits: Animals / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2014 Type: Article