Development of new therapy for malignant bone and soft tissue tumor by targeting bone marrow stromal cells

• Project/Area Number: 15K10449
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kyushu University
• Principal Investigator: Matsumoto Yoshihiro 九州大学, 医学研究院, 准教授 (10346794)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 骨軟部腫瘍 / 骨髄間質細胞 / 整形外科 / 悪性骨軟部腫瘍 / 薬剤耐性 / 転移

Outline of Final Research Achievements

The clinical prognosis of localized malignant bone and soft tissue tumors are improved by systemic chemotherapy. However, the prognosis of the advanced cases of those tumors remains dismal. In this study, we investigated the roles of bone marrow stem cells (BMSC), as well as tumor cells, in the tumor biology of malignant bone and soft tissue tumors. We found that, in Ewing's sarcoma, cadherin-11 on BMSC regulated the bone metastasis of Ewing's sarcoma cells. We also proved that, in synovial sarcoma, the activation of Erk pathway was critical for the drug resistance for pazopanib, a multi-kinase inhibitor.

Research Products

• [Journal Article] Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor (2017)
  • Author(s): Fukushima Suguru、Endo Makoto、Matsumoto Yoshihiro、Fukushi Jun-ichi、Matsunobu Tomoya、Kawaguchi Ken-ichi、Setsu Nokitaka、IIda Keiichiro、Yokoyama Nobuhiko、Nakagawa Makoto、Yahiro Kenichiro、Oda Yoshinao、Iwamoto Yukihide、Nakashima Yasuharu
  • Journal Title: PLOS ONE Volume: 12 Issue: 5 Pages: 0178064-0178064
  • DOI: 10.1371/journal.pone.0178064
  • Peer Reviewed / Open Access
• [Journal Article] Activation of ERK1/2 Causes Pazopanib Resistance via Downregulation of DUSP6 in Synovial Sarcoma Cells (2017)
  • Author(s): Yokoyama N, Matsunobu T, Matsumoto Y, Fukushi J, Endo M, Hatano M, Nabeshima A, Fukushima S, Okada S, and Iwamoto Y
  • Journal Title: ScイエンチフィcRえぽrts Volume: 7 Issue: 1 Pages: 45332-45332
  • DOI: 10.1038/srep45332
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone. (2015)
  • Author(s): Hatano M, Matsumoto Y, Fukushi J, Matsunobu T, Endo M, Okada S, Iura K, Kamura S, Fujiwara T, Iida K, Fujiwara Y, Nabeshima A, Yokoyama N, Fukushima S, Oda Y, Iwamoto Y.
  • Journal Title: Clin Exp Metastasis. Volume: 32 Issue: 6 Pages: 579-591
  • DOI: 10.1007/s10585-015-9729-y
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways (2015)
  • Author(s): Nabeshima Y., Matsumoto Y., Iwamoto Y., et al
  • Journal Title: British J Cancer Volume: NA Issue: 3 Pages: 1-9
  • DOI: 10.1038/bjc.2014.637
  • Peer Reviewed / Open Access / Acknowledgement Compliant