Pancreatic stellate cells radioprotect pancreatic cancer cells through β1-integrin signaling

Tine S. Mantoni, Serena Lunardi, Osama Al-Assar, Atsushi Masamune, Thomas B. Brunner

Research output: Contribution to journalArticlepeer-review

123 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3453-3458
Number of pages6
JournalCancer Research
Volume71
Issue number10
DOIs
Publication statusPublished - 2011 May 15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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