title: Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. No effective therapy is currently available for PDAC because of the lack of understanding of the mechanisms leading to its growth and development. Inflammatory cells, particularly mast cells, have been shown to play key roles in some cancers. We carried out this study to test the hypothesis that mast cells in the tumor microenvironment are essential for PDAC tumorigenesis.
  
  
  METHODS
  The presence of inflammatory cells at various stages of PDAC development was determined in a spontaneous mouse model of PDAC (K-ras(G12V)). The importance of mast cells was determined using orthotopically implanted PDAC cells in mast cell-deficient Kit(w-sh/w-sh) mice and further confirmed by reconstitution of wild-type bone marrow-derived mast cells. Clinical relevance was assessed by correlating the presence of mast cells with clinical outcome in patients with PDAC.
  
  
  RESULTS
  In the spontaneous mouse model of PDAC (K-ras(G12V)), there was an early influx of mast cells to the tumor microenvironment. PDAC tumor growth was suppressed in mast cell-deficient Kit(w-sh/w-sh) mice, but aggressive PDAC growth was restored when PDAC cells were injected into mast cell-deficient mice reconstituted with wild-type bone marrow-derived mast cells. Mast cell infiltration into the tumor microenvironment was predictive of poor prognosis in patients with PDAC.
  
  
  CONCLUSIONS
  Mast cells play an important role in PDAC growth and development in mouse models and are indicative of poor prognosis in humans, which makes them a potential novel therapeutic target.
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. David.Chang@USOncology.com
authors: David Z
authors: DZ
authors: Chang
authors: Ying
authors: Y
authors: Ma
authors: Baoan
authors: B
authors: Ji
authors: Huamin
authors: H
authors: Wang
authors: Defeng
authors: D
authors: Deng
authors: Yan
authors: Y
authors: Liu
authors: James L
authors: JL
authors: Abbruzzese
authors: Yong-jun
authors: YJ
authors: Liu
authors: Craig D
authors: CD
authors: Logsdon
authors: Patrick
authors: P
authors: Hwu
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D011905:Genes, ras; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011379:Prognosis; D059016:Tumor Microenvironment / Q000276:immunology