Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Mantoni, TS; Lunardi, S; Al-Assar, O; Masamune, A; Brunner, TB.
Pancreatic stellate cells radioprotect pancreatic cancer cells through β1-integrin signaling.
Cancer Res. 2011; 71(10):3453-8
Doi: 10.1158/0008-5472.CAN-10-1633
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- Führende Autor*innen der Med Uni Graz
- Brunner Thomas Baptist
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Cell Line, Tumor - administration & dosage
- Cell Proliferation - administration & dosage
- Coculture Techniques - administration & dosage
- Female - administration & dosage
- Humans - administration & dosage
- Integrin beta1 - genetics
- Mice - administration & dosage
- Mice, Nude - administration & dosage
- Pancreatic Neoplasms - pathology, radiotherapy
- Pancreatic Stellate Cells - cytology
- Phenotype - administration & dosage
- Phosphatidylinositol 3-Kinases - metabolism
- RNA, Small Interfering - metabolism
- Signal Transduction - administration & dosage