Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells

K. Tajima, R. Ohashi, Y. Sekido, T. Hida, T. Nara, M. Hashimoto, S. Iwakami, K. Minakata, T. Yae, F. Takahashi, Hideyuki Saya, K. Takahashi

研究成果: Article

29 引用 (Scopus)

抄録

Malignant pleural mesothelioma (MPM) is resistant to chemotherapy and thus shows a dismal prognosis. Osteopontin (OPN), a secreted noncollagenous and phosphoprotein, is suggested to be involved in the pathogenesis of MPM. However, the precise role of OPN, especially in the multidrug resistance of MPM, remains to be elucidated. We therefore established stable transfectants (ACC-MESO-1/OPN), which constitutively express OPN, to determine its role in the chemoresistance observed in MPM. The introduction of the OPN gene provides MPM cells with upregulated multidrug resistance through the mechanism of enhanced hyaluronate (HA) binding. The expression of CD44 variant isoforms, which inhibit HA binding, significantly decreased in ACC-MESO-1/OPN cells in comparison to control transfectants. Interestingly, the inhibition of the HA-CD44 interaction abrogated multidrug resistance in the ACC-MESO-1/OPN, thus suggesting the involvement of the surviving signal emanating from the HA-CD44 interaction. An enhanced level of the p-Akt in ACC-MESO-1/OPN cells was observed, and was diminished by CD44 siRNA. Inhibition of the Akt phosphorylation increased in number of the cells underwent apoptosis induced by NVB, VP-16 and GEM. Collectively, these results indicate that OPN is strongly involved in multidrug resistance by enhancing the CD44 binding to HA.

元の言語English
ページ(範囲)1941-1951
ページ数11
ジャーナルOncogene
29
発行部数13
DOI
出版物ステータスPublished - 2010 4

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Osteopontin
Mesothelioma
Multiple Drug Resistance
Hyaluronic Acid
Phosphoproteins
Etoposide
Small Interfering RNA
Protein Isoforms
Cell Count
Phosphorylation
Malignant Mesothelioma
Apoptosis
Drug Therapy

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

これを引用

Tajima, K., Ohashi, R., Sekido, Y., Hida, T., Nara, T., Hashimoto, M., ... Takahashi, K. (2010). Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells. Oncogene, 29(13), 1941-1951. https://doi.org/10.1038/onc.2009.478

Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells. / Tajima, K.; Ohashi, R.; Sekido, Y.; Hida, T.; Nara, T.; Hashimoto, M.; Iwakami, S.; Minakata, K.; Yae, T.; Takahashi, F.; Saya, Hideyuki; Takahashi, K.

:: Oncogene, 巻 29, 番号 13, 04.2010, p. 1941-1951.

研究成果: Article

Tajima, K, Ohashi, R, Sekido, Y, Hida, T, Nara, T, Hashimoto, M, Iwakami, S, Minakata, K, Yae, T, Takahashi, F, Saya, H & Takahashi, K 2010, 'Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells', Oncogene, 巻. 29, 番号 13, pp. 1941-1951. https://doi.org/10.1038/onc.2009.478
Tajima K, Ohashi R, Sekido Y, Hida T, Nara T, Hashimoto M その他. Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells. Oncogene. 2010 4;29(13):1941-1951. https://doi.org/10.1038/onc.2009.478
Tajima, K. ; Ohashi, R. ; Sekido, Y. ; Hida, T. ; Nara, T. ; Hashimoto, M. ; Iwakami, S. ; Minakata, K. ; Yae, T. ; Takahashi, F. ; Saya, Hideyuki ; Takahashi, K. / Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells. :: Oncogene. 2010 ; 巻 29, 番号 13. pp. 1941-1951.
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abstract = "Malignant pleural mesothelioma (MPM) is resistant to chemotherapy and thus shows a dismal prognosis. Osteopontin (OPN), a secreted noncollagenous and phosphoprotein, is suggested to be involved in the pathogenesis of MPM. However, the precise role of OPN, especially in the multidrug resistance of MPM, remains to be elucidated. We therefore established stable transfectants (ACC-MESO-1/OPN), which constitutively express OPN, to determine its role in the chemoresistance observed in MPM. The introduction of the OPN gene provides MPM cells with upregulated multidrug resistance through the mechanism of enhanced hyaluronate (HA) binding. The expression of CD44 variant isoforms, which inhibit HA binding, significantly decreased in ACC-MESO-1/OPN cells in comparison to control transfectants. Interestingly, the inhibition of the HA-CD44 interaction abrogated multidrug resistance in the ACC-MESO-1/OPN, thus suggesting the involvement of the surviving signal emanating from the HA-CD44 interaction. An enhanced level of the p-Akt in ACC-MESO-1/OPN cells was observed, and was diminished by CD44 siRNA. Inhibition of the Akt phosphorylation increased in number of the cells underwent apoptosis induced by NVB, VP-16 and GEM. Collectively, these results indicate that OPN is strongly involved in multidrug resistance by enhancing the CD44 binding to HA.",
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AU - Nara, T.

AU - Hashimoto, M.

AU - Iwakami, S.

AU - Minakata, K.

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AU - Saya, Hideyuki

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