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Published on: April 6, 2016
Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines
Ling Xu1, Martin Hausmann, Wolfgang Dietmaier
1Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany.
Background:
Cholangiocarcinoma (CC) is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro.
Methods:
Expression of EGFR (epithelial growth factor receptor), HGFR (hepatocyte growth factor receptor) IGF1R (insulin-like growth factor 1 receptor), IGF2R (insulin-like growth factor 2 receptor) and VEGFR1-3 (vascular endothelial growth factor receptor 1-3) were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1). The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations.
Results:
EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml), with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D). HuH28, OZ and TFK-1 lacked KRAS mutation.
Conclusion:
CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab.
Insights
Cholangiocarcinoma cell lines express various growth factor receptors. While EGFR (epithelial growth factor receptor) targeting with cetuximab showed varied effects, KRAS mutations may influence treatment response in this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Cholangiocarcinoma (CC) is a bile duct and gallbladder cancer.
- Targeting growth factor receptors shows promise in solid tumors.
- Understanding receptor expression in CC is crucial for targeted therapies.
Purpose of the Study:
- To determine the expression of seven growth factor receptors in human CC cell lines.
- To assess the in vitro effect of blocking the epidermal growth factor receptor (EGFR) using cetuximab.
- To investigate the role of KRAS mutations in CC cell line response to EGFR inhibition.
Main Methods:
- Examined expression of EGFR, HGFR, IGF1R, IGF2R, and VEGFR1-3 in four CC cell lines (EGI-1, HuH28, OZ, TFK-1).
- Assessed cetuximab's effect on cell growth and apoptosis.
- Screened cell lines for KRAS mutations.
Main Results:
- EGFR, HGFR, and IGF1R were expressed in all tested CC cell lines.
- Cetuximab inhibited growth in TFK-1 cells and increased apoptosis at high doses, but not in EGI-1 cells.
- EGI-1 cells harbored a KRAS mutation, while HuH28, OZ, and TFK-1 cells did not.
Conclusions:
- CC cell lines exhibit diverse growth factor receptor expression patterns.
- KRAS genotype may impact the efficacy of growth factor inhibitor therapies in CC.
- EGFR expression alone does not predict cetuximab treatment response.
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