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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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June-2014 Volume 44 Issue 6

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International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

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International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Article

Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed

  • Authors:
    • Susumu Takeuchi
    • Masahiro Seike
    • Rintaro Noro
    • Chie Soeno
    • Teppei Sugano
    • Fenfei Zou
    • Haruka Uesaka
    • Nobuhiko Nishijima
    • Masaru Matsumoto
    • Yuji Minegishi
    • Kaoru Kubota
    • Akihiko Gemma
  • View Affiliations / Copyright

    Affiliations: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan, MediBIC Group, Tokyo 102-8578, Japan
  • Pages: 1886-1894
    |
    Published online on: April 7, 2014
       https://doi.org/10.3892/ijo.2014.2370
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Abstract

Pemetrexed (PEM) is currently recommended as one of the standard anticancer drugs for malignant pleural mesothelioma (MPM). However, the mechanism of the sensitivity of MPM to PEM remains unclear. We analyzed the antitumor effects of PEM in six MPM cell lines by MTS assay. To identify genes associated with drug sensitivity, we conducted gene expression profiling on the same set of cell lines using GeneChips and pathway analysis. Three cell lines were sensitive to PEM. A total fo 18 transcripts and 14 genes identified by GeneChips were significantly correlated with sensitivity to PEM. Pathway analysis revealed that osteopontin (SPP1/OPN) was an important target in PEM sensitivity. Overexpression of SPP1/OPN was observed in the sensitive cells by quantitative PCR and western blot analysis. Introduction of SPP1/OPN by lentiviral vector significantly enhanced the invasion activities of MPM cells. PEM treatment with SPP1/OPN knockdown inhibited the PEM-induced cell growth-inhibitory effect in PEM-sensitive cells. Expression of SPP1/OPN and AKT phosphorylation significantly decreased after PEM treatment of the PEM-sensitive cells. High immunohistochemical expression of SPP1/OPN was observed in two of three MPM patients who had a partial response to PEM-based chemotherapy. PEM has antitumor effects in MPM cells dependent on SPP1/OPN overexpression resulting in AKT activation. Our results suggest that SPP1 may be used as a single predictive biomarker of the effectiveness of PEM treatment in MPM.
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Copy and paste a formatted citation
Spandidos Publications style
Takeuchi S, Seike M, Noro R, Soeno C, Sugano T, Zou F, Uesaka H, Nishijima N, Matsumoto M, Minegishi Y, Minegishi Y, et al: Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed. Int J Oncol 44: 1886-1894, 2014.
APA
Takeuchi, S., Seike, M., Noro, R., Soeno, C., Sugano, T., Zou, F. ... Gemma, A. (2014). Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed. International Journal of Oncology, 44, 1886-1894. https://doi.org/10.3892/ijo.2014.2370
MLA
Takeuchi, S., Seike, M., Noro, R., Soeno, C., Sugano, T., Zou, F., Uesaka, H., Nishijima, N., Matsumoto, M., Minegishi, Y., Kubota, K., Gemma, A."Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed". International Journal of Oncology 44.6 (2014): 1886-1894.
Chicago
Takeuchi, S., Seike, M., Noro, R., Soeno, C., Sugano, T., Zou, F., Uesaka, H., Nishijima, N., Matsumoto, M., Minegishi, Y., Kubota, K., Gemma, A."Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed". International Journal of Oncology 44, no. 6 (2014): 1886-1894. https://doi.org/10.3892/ijo.2014.2370
Copy and paste a formatted citation
x
Spandidos Publications style
Takeuchi S, Seike M, Noro R, Soeno C, Sugano T, Zou F, Uesaka H, Nishijima N, Matsumoto M, Minegishi Y, Minegishi Y, et al: Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed. Int J Oncol 44: 1886-1894, 2014.
APA
Takeuchi, S., Seike, M., Noro, R., Soeno, C., Sugano, T., Zou, F. ... Gemma, A. (2014). Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed. International Journal of Oncology, 44, 1886-1894. https://doi.org/10.3892/ijo.2014.2370
MLA
Takeuchi, S., Seike, M., Noro, R., Soeno, C., Sugano, T., Zou, F., Uesaka, H., Nishijima, N., Matsumoto, M., Minegishi, Y., Kubota, K., Gemma, A."Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed". International Journal of Oncology 44.6 (2014): 1886-1894.
Chicago
Takeuchi, S., Seike, M., Noro, R., Soeno, C., Sugano, T., Zou, F., Uesaka, H., Nishijima, N., Matsumoto, M., Minegishi, Y., Kubota, K., Gemma, A."Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed". International Journal of Oncology 44, no. 6 (2014): 1886-1894. https://doi.org/10.3892/ijo.2014.2370
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