Interaction between human osteosarcoma cells and mesenchymal stem cells via IL-8 signaling in tumor microenvironment.

• Project/Area Number: 16K10866
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Oita University
• Principal Investigator: Itonaga Ichiro 大分大学, 医学部, 講師 (10295181)
• Co-Investigator(Kenkyū-buntansha): 池田 真一 大分大学, 医学部, 助教 (70444883)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); 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)
• Keywords: 骨肉腫 / 間葉系幹細胞 / 液性因子

Outline of Final Research Achievements

Osteosarcoma (OS) is the representative primary malignant bone tumor with the highest incidence. It is known that malignant phenotypes of OS, such as proliferation, invasion, and metastasis, are significantly influenced not only by characteristics of the tumor itself, but also by the surrounding microenvironment. In other words, OS is considered to utilize cells in the vicinity of the tumor by changing the characteristics of these cells. Direct intercellular contact is believed to be important for this phenomenon. In the present study, we hypothesized that an interaction mediated by a humoral factor, requiring no cellular contact, might play a significant role in the progression of OS.

Academic Significance and Societal Importance of the Research Achievements

骨肉腫細胞がより効率的に微小環境さらには遠隔転移先の状態を好腫瘍性に改変するために、液性因子が中心的に使われていると予想した。この相互作用が広範囲に拡散できる液性因子を介するものであれば、腫瘍拡大のための環境整備において格段に有利なはずであり、このような性質を獲得できた細胞が選択的に進展していく可能性が高いと思われる。本研究の仮説が実証されれば、骨肉腫の浸潤・転移における新たな分子機構が明らかとなるのみならず、このサイクルを遮断する新しい治療戦略の開発にも繋がると考えられ、本研究の意義は極めて大きいと考える。

Research Products

• [Journal Article] Surrogacy of intermediate endpoints for overall survival in randomized controlled trials of first-line treatment for advanced soft tissue sarcoma in the pre- and post-pazopanib era: a meta-analytic evaluation. (2019)
  • Author(s): Tanaka K, Kawano M, Iwasaki T, Itonaga I, Tsumura H.
  • Journal Title: BMC Cancer. Volume: 19 Issue: 1 Pages: 56-56
  • DOI: 10.1186/s12885-019-5268-2
  • Peer Reviewed / Open Access
• [Journal Article] A meta-analysis of randomized controlled trials that compare standard doxorubicin with other first-line chemotherapies for advanced/metastatic soft tissue sarcomas. (2019)
  • Author(s): Tanaka K, Kawano M, Iwasaki T, Itonaga I, Tsumura H.
  • Journal Title: PLoS One Volume: 14 Issue: 1 Pages: 1-18
  • DOI: 10.1371/journal.pone.0210671
  • Peer Reviewed / Open Access
• [Journal Article] Interaction between human osteosarcoma and mesenchymal stem cells via an interleukin-8 signaling loop in the tumor microenvironment. (2018)
  • Author(s): Kawano M, Tanaka K, Itonaga I, Iwasaki T, Tsumura H.
  • Journal Title: Cell Commun Signal. Volume: 16(1) Issue: 1 Pages: 13-13
  • DOI: 10.1186/s12964-018-0225-2
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-181c prevents apoptosis by targeting of FAS receptor in Ewing's sarcoma cells. (2018)
  • Author(s): Kawano M, Tanaka K, Itonaga I, Iwasaki T, Tsumura H.
  • Journal Title: Cancer Cell Int. Volume: 18 Issue: 1 Pages: 37-37
  • DOI: 10.1186/s12935-018-0536-9
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-20b promotes cell proliferation via targeting of TGF-β receptor II and upregulates MYC expression in Ewing's sarcoma cells. (2017)
  • Author(s): Kawano M, Tanaka K, Itonaga I, Iwasaki T, Tsumura H.
  • Journal Title: Int J Oncol. Volume: 51(6) Issue: 6 Pages: 1842-1850
  • DOI: 10.3892/ijo.2017.4155
  • Peer Reviewed / Open Access