Caveolin-1 mediated radioresistance of 3D grown pancreatic cancer cells
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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, 0-6 Gy). 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 β1 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.
Details
Original language | English |
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Pages (from-to) | 362-370 |
Number of pages | 9 |
Journal | Radiotherapy and oncology |
Volume | 92 |
Issue number | 3 |
Publication status | Published - Sept 2009 |
Peer-reviewed | Yes |
External IDs
PubMed | 19665245 |
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ORCID | /0000-0001-5684-629X/work/162348810 |
Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- β1 integrin, Caveolin-1, Ionizing radiation, Pancreatic carcinoma, Three-dimensional cell culture