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Open Access Research article

Imatinib mesylate inhibits cell growth of malignant peripheral nerve sheath tumors in vitro and in vivo through suppression of PDGFR-β

Jun Ohishi12, Mikiko Aoki1, Kazuki Nabeshima1*, Junji Suzumiya3, Tamotsu Takeuchi4, Akira Ogose5, Michiyuki Hakozaki6, Yuichi Yamashita2 and Hiroshi Iwasaki1

Author Affiliations

1 Department of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

2 Gastroenterological Surgery, Fukuoka University School of Medicine, Fukuoka, Japan

3 Shimane University Hospital Cancer Center, Shimane, Japan

4 Department of Immunopathology, University School of Medicine, Gifu, Japan

5 Division of Orthopaedic Surgery, Department of Regenerative Transplant Medicine, Niigata University Graduate School of Medicine and Dental Science, Niigata, Japan

6 Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan

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BMC Cancer 2013, 13:224  doi:10.1186/1471-2407-13-224

Published: 4 May 2013

Abstract

Background

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive and associated with poor prognosis. Basic research to develop new treatment regimens is critically needed.

Methods

The effects of imatinib mesylate on MPNSTs were examined in six human MPNST cell lines and in a xenograft mouse model.

Results

The results showed expression of platelet-derived growth factor receptor-β and suppression of its phosphorylation by imatinib mesylate in all six cell lines. Imatinib mesylate effectively suppressed MPNST cell growth in vitro at concentrations similar to those used clinically (1.46 − 4.6 μM) in three of six cell lines. Knockdown of PDGFR-β by transfection with a specific siRNA also caused significant reduction in cell proliferation in the sensitive cell lines, but not in the resistant cell lines. Furthermore, imatinib mesylate also significantly suppressed colony formation within soft agar and tumor growth in xenograft models using two of the three sensitive MPNST cell lines. There was excellent agreement between in vitro and in vivo sensitivity to imatinib mesylate, suggesting possible selection of imatinib-sensitive tumors by in vitro analysis.

Conclusions

The results suggest that imatinib mesylate may be useful in the treatment of MPNST patients and in vitro studies may help select cells that are sensitive to imatinib mesylate in vivo.