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Pancreatic stellate cells radioprotect pancreatic cancer cells through ?1-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 ?1-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 ?1-integrin-dependent manner.

SUBMITTER: Mantoni TS

PROVIDER: S-EPMC3097171 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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

Mantoni Tine S TS Lunardi Serena S Al-Assar Osama O Masamune Atsushi A Brunner Thomas B TB

Cancer research 20110510 10

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 ...[more]

PMID: 21558392

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