Association of amphiregulin with the cetuximab sensitivity of gastric cancer cell lines

  • Authors:
    • Julia Kneissl
    • Simone Keller
    • Thomas Lorber
    • Stefan Heindl
    • Gisela Keller
    • Ingo Drexler
    • Alexander Hapfelmeier
    • Heinz Höfler
    • Birgit Luber
  • View Affiliations

  • Published online on: May 14, 2012     https://doi.org/10.3892/ijo.2012.1479
  • Pages: 733-744
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Abstract

The therapeutic activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab in gastric cancer is currently being investigated in clinical studies. Reliable biomarkers for the identification of patients who are likely to benefit from this treatment are not available. In this study, we assessed the activity of cetuximab in five gastric cancer cell lines (AGS, AZ521, Hs746T, LMSU and MKN1). The viability of two of these cell lines, AZ521 and MKN1, was significantly reduced by cetuximab treatment. High expression and secretion levels of the EGFR-binding ligand, amphiregulin (AREG), were associated with cetuximab responsiveness. MET activation and mutations in Kirsten-Ras gene (KRAS) were associated with cetuximab resistance. By introducing a hierarchy between these markers, we established a model that facilitated the correct classification of all five gastric cancer cell lines as cetuximab responsive or non-responsive. The highest priority was allocated to activating KRAS mutations, followed by MET activation and finally by the levels of secreted AREG. In order to validate these results, we used three additional human gastric cancer cell lines (KATOIII, MKN28 and MKN45). In conclusion, we propose that our model allows the response of gastric cancer cell lines to cetuximab treatment to be predicted.
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August 2012
Volume 41 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kneissl J, Keller S, Lorber T, Heindl S, Keller G, Drexler I, Hapfelmeier A, Höfler H and Luber B: Association of amphiregulin with the cetuximab sensitivity of gastric cancer cell lines. Int J Oncol 41: 733-744, 2012.
APA
Kneissl, J., Keller, S., Lorber, T., Heindl, S., Keller, G., Drexler, I. ... Luber, B. (2012). Association of amphiregulin with the cetuximab sensitivity of gastric cancer cell lines. International Journal of Oncology, 41, 733-744. https://doi.org/10.3892/ijo.2012.1479
MLA
Kneissl, J., Keller, S., Lorber, T., Heindl, S., Keller, G., Drexler, I., Hapfelmeier, A., Höfler, H., Luber, B."Association of amphiregulin with the cetuximab sensitivity of gastric cancer cell lines". International Journal of Oncology 41.2 (2012): 733-744.
Chicago
Kneissl, J., Keller, S., Lorber, T., Heindl, S., Keller, G., Drexler, I., Hapfelmeier, A., Höfler, H., Luber, B."Association of amphiregulin with the cetuximab sensitivity of gastric cancer cell lines". International Journal of Oncology 41, no. 2 (2012): 733-744. https://doi.org/10.3892/ijo.2012.1479