title: Dynamic mast cell-stromal cell interactions promote growth of pancreatic cancer.
abstract: Pancreatic ductal adenocarcinoma (PDAC) exists in a complex desmoplastic microenvironment, which includes cancer-associated fibroblasts [also known as pancreatic stellate cells (PSC)] and immune cells that provide a fibrotic niche that impedes successful cancer therapy. We have found that mast cells are essential for PDAC tumorigenesis. Whether mast cells contribute to the growth of PDAC and/or PSCs is unknown. Here, we tested the hypothesis that mast cells contribute to the growth of PSCs and tumor cells, thus contributing to PDAC development. Tumor cells promoted mast cell migration. Both tumor cells and PSCs stimulated mast cell activation. Conversely, mast cell-derived interleukin (IL)-13 and tryptase stimulated PSC proliferation. Treating tumor-bearing mice with agents that block mast cell migration and function depressed PDAC growth. Our findings suggest that mast cells exacerbate the cellular and extracellular dynamics of the tumor microenvironment found in PDAC. Therefore, targeting mast cells may inhibit stromal formation and improve therapy.
authors: Department of Immunology and the Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Ying
authors: Y
authors: Ma
authors: Rosa F
authors: RF
authors: Hwang
authors: Craig D
authors: CD
authors: Logsdon
authors: Stephen E
authors: SE
authors: Ullrich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001596:Benzylamines; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D000080027:Cyclams; D004847:Epithelial Cells / Q000502:physiology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D018793:Interleukin-13 / Q000502:physiology; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000502:physiology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D017154:Stromal Cells / Q000502:physiology*; D053802:Tryptases / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001596:Benzylamines; D017077:Culture Media, Conditioned; D000080027:Cyclams; D006571:Heterocyclic Compounds; D018793:Interleukin-13; D019718:Receptors, CXCR4; D053802:Tryptases; C088327:plerixafor
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