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Article Open Access

Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells

  • Authors:
    • Riki Okita
    • Katsuhiko Shimizu
    • Yuji Nojima
    • Takuro Yukawa
    • Ai Maeda
    • Shinsuke Saisho
    • Masao Nakata
  • View Affiliations / Copyright

    Affiliations: Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki 701-0192, Japan
    Copyright: © Okita et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2864-2870
    |
    Published online on: September 28, 2015
       https://doi.org/10.3892/or.2015.4314
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Abstract

EGFR/HER2 are frequently expressed in MPM tissues, however, no studies have shown the clinical benefit of using EGFR/HER2-targeting drugs in patients with malignant pleural mesothelioma (MPM). It was reported that the tyrosine kinase inhibitor (TKI) lapatinib enhanced trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC) in HER2-positive breast cancer, suggesting that this combination is a promising strategy for MPM treatment. The aim of the present study was to explore the possibility of a TKI combined with trastuzumab to enhance ADCC in MPM cells. Five MPM cell lines were used to test the effects of TKIs targeting EGFR (gefitinib, afatinib and lapatinib) on cell proliferation and the expression of the HER family receptor. The combined effects of TKI with trastuzumab on ADCC were evaluated using the LDH release assay. Additionally, MPM cells were isolated from patients and evaluated for lapatinib-induced upregulation of HER family receptors and trastuzumab- or cetuximab‑mediated ADCC. In MPM cell lines, HER2 expression was upregulated by lapatinib, downregulated by afatinib and unaffected by gefitinib. As expected, more trastuzumab bound to MPM cells pretreated with lapatinib than untreated cells, resulting in the enhancement of trastuzumab-mediated ADCC in MPM cells. In patient-derived MPM cells, both HER2 and EGFR were upregulated by lapatinib, resulting in the enhancement of both trastuzumab- and cetuximab-mediated ADCC. Of the three TKIs, only lapatinib enhanced trastuzumab-mediated ADCC via the upregulation of HER2 expression in MPM cells, suggesting that sequential combination of lapatinib and trastuzumab may be a promising strategy for MPM treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Okita R, Shimizu K, Nojima Y, Yukawa T, Maeda A, Saisho S and Nakata M: Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells. Oncol Rep 34: 2864-2870, 2015.
APA
Okita, R., Shimizu, K., Nojima, Y., Yukawa, T., Maeda, A., Saisho, S., & Nakata, M. (2015). Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells. Oncology Reports, 34, 2864-2870. https://doi.org/10.3892/or.2015.4314
MLA
Okita, R., Shimizu, K., Nojima, Y., Yukawa, T., Maeda, A., Saisho, S., Nakata, M."Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells". Oncology Reports 34.6 (2015): 2864-2870.
Chicago
Okita, R., Shimizu, K., Nojima, Y., Yukawa, T., Maeda, A., Saisho, S., Nakata, M."Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells". Oncology Reports 34, no. 6 (2015): 2864-2870. https://doi.org/10.3892/or.2015.4314
Copy and paste a formatted citation
x
Spandidos Publications style
Okita R, Shimizu K, Nojima Y, Yukawa T, Maeda A, Saisho S and Nakata M: Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells. Oncol Rep 34: 2864-2870, 2015.
APA
Okita, R., Shimizu, K., Nojima, Y., Yukawa, T., Maeda, A., Saisho, S., & Nakata, M. (2015). Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells. Oncology Reports, 34, 2864-2870. https://doi.org/10.3892/or.2015.4314
MLA
Okita, R., Shimizu, K., Nojima, Y., Yukawa, T., Maeda, A., Saisho, S., Nakata, M."Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells". Oncology Reports 34.6 (2015): 2864-2870.
Chicago
Okita, R., Shimizu, K., Nojima, Y., Yukawa, T., Maeda, A., Saisho, S., Nakata, M."Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells". Oncology Reports 34, no. 6 (2015): 2864-2870. https://doi.org/10.3892/or.2015.4314
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