Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

Ling Xu12, Martin Hausmann13, Wolfgang Dietmaier4, Silvia Kellermeier13, Theresa Pesch3, Manuela Stieber-Gunckel1, Elisabeth Lippert1, Frank Klebl1 and Gerhard Rogler13*

Author Affiliations

1 Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany

2 Department of Medical Oncology, Peking University First Hospital, 100034 Peking, China

3 Clinic of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital of Zürich, 8091 Zürich, Switzerland

4 Department of Pathology, University of Regensburg, 93042 Regensburg, Germany

For all author emails, please log on.

BMC Cancer 2010, 10:302  doi:10.1186/1471-2407-10-302

Published: 18 June 2010

Abstract

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.