Document Detail

Caveolin-1 mediated radioresistance of 3D grown pancreatic cancer cells.
MedLine Citation:
PMID:  19665245     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: Resistance of pancreatic ductal adenocarcinoma (PDAC) to chemo- and radiotherapy is a major obstacle. The integral membrane protein Caveolin-1 (Cav-1) has been suggested as a potent target in human pancreatic carcinoma cells. MATERIALS AND METHODS: Human pancreatic tumor cells were examined in a three-dimensional (3D) cell culture model with regard to clonogenic survival, apoptosis, radiogenic DNA-double strand breaks and protein expression and phosphorylation under siRNA-mediated knockdown of Cav-1 without and in combination with irradiation (X-rays, 0-6Gy). Immunohistochemistry was used to assess Cav-1 expression in biopsies from patients with PDAC. RESULTS: Tumor cells in PDAC showed significantly higher Cav-1 expression relative to tumor stroma. Cav-1 knockdown significantly reduced beta1 integrin expression and Akt phosphorylation, induced Caspase 3- and Caspase 8-dependent apoptosis and enhanced the radiosensitivity of 3D cell cultures. While cell cycling and Cav-1 promoter activity remained stable, Cav-1 knockdown-induced radiosensitization correlated with elevated numbers of residual DNA-double strand breaks. CONCLUSIONS: Our data strongly support the concept of Cav-1 as a potent target in pancreatic carcinoma cells due to radiosensitization and Cav-1 overexpression in tumor cells of PDAC. 3D cell cultures are powerful and useful tools for the testing of novel targeting strategies to optimize conventional radio- and chemotherapy regimes for PDAC.
Stephanie Hehlgans; Iris Eke; Katja Storch; Michael Haase; Gustavo B Baretton; Nils Cordes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-06
Journal Detail:
Title:  Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology     Volume:  92     ISSN:  1879-0887     ISO Abbreviation:  Radiother Oncol     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-15     Completed Date:  2010-01-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8407192     Medline TA:  Radiother Oncol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  362-70     Citation Subset:  IM    
OncoRay-Center for Radiation Research in Oncology, Dresden University of Technology, Dresden, Germany.
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MeSH Terms
Antigens, CD29 / genetics,  metabolism*
Apoptosis / genetics,  physiology
Carcinoma, Pancreatic Ductal / drug therapy,  radiotherapy
Caveolin 1 / genetics,  metabolism*
Cell Cycle / genetics,  radiation effects*
Cell Line, Tumor / cytology,  drug effects,  radiation effects
Cell Proliferation / drug effects,  radiation effects
Gene Expression Regulation, Neoplastic
Pancreatic Neoplasms / drug therapy,  radiotherapy
Phosphorylation / genetics,  radiation effects
RNA, Small Interfering / genetics,  metabolism*
Radiation Tolerance*
Radiation, Ionizing
Reference Values
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects,  genetics
Stem Cells / drug effects,  radiation effects
Reg. No./Substance:
0/Antigens, CD29; 0/Caveolin 1; 0/RNA, Small Interfering

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