title: Pancreatic stellate cells radioprotect pancreatic cancer cells through β1-integrin signaling.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a strong desmoplastic reaction where the stromal compartment often accounts for more than half of the tumor volume. Pancreatic stellate cells (PSC) are a central mediator of desmoplasia. There is increasing evidence that desmoplasia is contributing to the poor therapeutic response of PDAC. We show that PSCs promote radioprotection and stimulate proliferation in pancreatic cancer cells (PCC) in direct coculture. Our in vivo studies show PSC-dependent radioprotection in response to a single dose and to fractionated radiation. Abrogating β1-integrin signaling abolishes the PSC-mediated radioprotection in PCCs. Furthermore, this effect is independent of PI3K (phosphoinositide 3-kinase) but dependent on FAK. Taken together, we show for the first time that PSCs promote radioprotection of PCCs in a β1-integrin-dependent manner.
authors.affiliation: Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, United Kingdom.
authors.forename: Tine S
authors.initials: TS
authors.lastname: Mantoni
authors.forename: Serena
authors.initials: S
authors.lastname: Lunardi
authors.forename: Osama
authors.initials: O
authors.lastname: Al-Assar
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masamune
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Brunner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D058954:Pancreatic Stellate Cells / Q000166:cytology*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019012:Integrin beta1; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases