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

• Published in: BMC cancer Vol. 10; no. 1; p. 302
• Main Authors: Xu, Ling, Hausmann, Martin, Dietmaier, Wolfgang, Kellermeier, Silvia, Pesch, Theresa, Stieber-Gunckel, Manuela, Lippert, Elisabeth, Klebl, Frank, Rogler, Gerhard
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18-06-2010; BioMed Central; BMC
• Subjects: Acquisitions & mergers; Amino acids; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - metabolism; Bile Duct Neoplasms - pathology; Bile Ducts, Intrahepatic - drug effects; Bile Ducts, Intrahepatic - metabolism; Bile Ducts, Intrahepatic - pathology; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cetuximab; Chemotherapy; Cholangiocarcinoma - genetics; Cholangiocarcinoma - metabolism; Cholangiocarcinoma - pathology; Colleges & universities; Dose-Response Relationship, Drug; Experiments; Gene Expression Regulation, Neoplastic; Gene mutations; Health aspects; Health sciences; Hepatology; Hospitals; Humans; Insulin; Insulin-like growth factors; Internal medicine; Mutation; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-met - metabolism; Proto-Oncogene Proteins p21(ras); Quality of life; ras Proteins - genetics; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Receptors, Growth Factor - metabolism; Receptors, Somatomedin - metabolism; Receptors, Vascular Endothelial Growth Factor - metabolism; RNA, Messenger - metabolism; Rodents; Time Factors; Switzerland; China; Germany
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-10-302

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.
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.
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.
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.