Expression of Epidermal Growth Factor Receptor Detected by Cetuximab Indicates Its Efficacy to Inhibit In Vitro and In Vivo Proliferation of Colorectal Cancer Cells

Kohei Shigeta, Tetsu Hayashida, Yoshinori Hoshino, Koji Okabayashi, Takashi Endo, Yoshiyuki Ishii, Hirotoshi Hasegawa, Yuukou Kitagawa

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Abstract

Cetuximab is a chimeric mouse-human monoclonal antibody that targets the human epidermal growth factor receptor (EGFR). However, EGFR expression determined by immunohistochemistry does not predict clinical outcomes of colorectal cancer (CRC) patients treated with cetuximab. Therefore, we evaluated the correlation between EGFR levels detected by cetuximab and drug sensitivities of CRC cell lines (Caco-2, WiDR, SW480, and HCT116) and the A431 epidermoid carcinoma cell line. We used flow cytometry (FCM) to detect EGFR-binding of biotinylated cetuximab on the cell surface. Subcloned cell lines showing the highest and lowest EGFR expression levels were chosen for further study. Cytotoxic assays were used to determine differential responses to cetuximab. Xenograft models treated with cetuximab intraperitoneally to assess sensitivity to cetuximab. Strong responses to cetuximab were specifically exhibited by subcloned cells with high EGFR expression levels. Furthermore, cetuximab inhibited the growth of tumors in xenograft models with high or low EGFR expression levels by 35% and 10%-20%, respectively. We conclude that detection of EGFR expression by cetuximab promises to provide a novel, sensitive, and specific method for predicting the sensitivity of CRC to cetuximab.

Original languageEnglish
Article numbere66302
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - 2013 Jun 18

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colorectal neoplasms
Epidermal Growth Factor Receptor
Colorectal Neoplasms
Cells
cell lines
Heterografts
Cell Line
In Vitro Techniques
Cetuximab
epidermal growth factor receptors
neoplasm cells
carcinoma
immunohistochemistry
flow cytometry
Flow cytometry
monoclonal antibodies
cells
drugs
Tumors
Squamous Cell Carcinoma

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Expression of Epidermal Growth Factor Receptor Detected by Cetuximab Indicates Its Efficacy to Inhibit In Vitro and In Vivo Proliferation of Colorectal Cancer Cells. / Shigeta, Kohei; Hayashida, Tetsu; Hoshino, Yoshinori; Okabayashi, Koji; Endo, Takashi; Ishii, Yoshiyuki; Hasegawa, Hirotoshi; Kitagawa, Yuukou.

In: PLoS One, Vol. 8, No. 6, e66302, 18.06.2013.

Research output: Contribution to journalArticle

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