Autocrine epidermal growth factor receptor ligand production and cetuximab response in head and neck squamous cell carcinoma cell lines

J Cancer Res Clin Oncol. 2012 Mar;138(3):491-9. doi: 10.1007/s00432-011-1127-5. Epub 2011 Dec 23.


Purpose: Predictive strategies for the treatment efficacy of cetuximab are currently not available for head and neck cancer. We investigated the correlation between the expression of epidermal growth factor receptor (EGFR) ligands and EGFR expression, and the growth inhibitory activity of cetuximab in a panel of head and neck squamous cell carcinoma (HNSCC) cell lines.

Methods: The growth inhibiting effect of cetuximab was measured for eight HNSCC cell lines and correlated with the autocrine production of five EGFR ligands as measured by ELISA, and the mRNA expression of two ligands, as measured by quantitative RT-PCR. EGFR expression was assessed by western blot analysis.

Results: There was a good correlation between the expression of four of the EGFR ligands (TGF-α, amphiregulin, epiregulin and epigen) and the growth inhibiting effect of cetuximab. TGF-α had the highest predictive potential but had to be combined with epigen for full prediction. EGFR expression also correlated with cetuximab sensitivity but less clearly.

Conclusions: The results indicate that the expression of several EGFR ligands has to be used to predict sensitivity to cetuximab in HNSCC. This has to be further evaluated in clinical samples.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphiregulin
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line, Tumor
  • Cetuximab
  • EGF Family of Proteins
  • Enzyme-Linked Immunosorbent Assay
  • Epidermal Growth Factor / biosynthesis*
  • Epigen
  • Epiregulin
  • ErbB Receptors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / biosynthesis
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Ligands
  • Predictive Value of Tests
  • Reverse Transcriptase Polymerase Chain Reaction
  • Squamous Cell Carcinoma of Head and Neck
  • Transforming Growth Factor alpha / biosynthesis*


  • AREG protein, human
  • Amphiregulin
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • EGF Family of Proteins
  • EPGN protein, human
  • EREG protein, human
  • Epigen
  • Epiregulin
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Transforming Growth Factor alpha
  • Epidermal Growth Factor
  • ErbB Receptors
  • Cetuximab