Establishment of a murine soft tissue sarcoma cell line with high metastatic potential to the lung

• Project/Area Number: 24592233
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Osaka University
• Principal Investigator: NAKA Norifumi 大阪大学, 医学(系)研究科(研究院), 講師 (90601964)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Hideki 大阪大学, 大学院医学系研究科, 教授 (60191558)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 骨軟部腫瘍 / 肉腫細胞株 / 実験動物モデル / 転移能 / plexin / semaphorin / 動物実験モデル / 整形外科

Outline of Final Research Achievements

We established a murine soft tissue sarcoma cell line (TR6BC1-LM) with high metastatic potential to the lung from benign murine neurogenic cell line (TR6BC1) using repeated Fidler’s procedures. Compared to TR6BC1, TR6BC1-LM exhibits higher in vitro 3D growth ability, rapid in vivo tumor formation property and enhanced invasive potential. Semaphorin4D/PlexinB1 signaling known as guidance signals in development was activated in this cell line. PlexinB1 silencing induced attenuation of motility and invasiveness of TR6BC1-LM. These data suggest that activation of Semaphorin4D/PlexinB1 signaling might confer high metastatic capacity on this cell line.

Research Products

• [Journal Article] Tailored therapeutic strategies for synovial sarcoma : Receptor tyrosine kinase pathway analyses predict sensitivity to the mTOR inhibitor RAD001 (2014)
  • Author(s): Yasui, H., Naka, N., Imura, Y., Outani, H., Kaneko, K., Hamada, KI., Sasagawa, S., Araki, N., Ueda, T., Itoh, K., Myoui, A., and Yoshikawa, H
  • Journal Title: Cancer Lett Volume: 347(1) Issue: 1 Pages: 114-122
  • DOI: 10.1016/j.canlet.2014.01.027
  • Peer Reviewed
• [Journal Article] Expression of noggin, an antagonist of bone morphogenetic protein, in schwannoma: A possible mechanism. (2014)
  • Author(s): Kaneko K, Higuchi C, Naka N, Yoshikawa H.
  • Journal Title: Oncol Lett Volume: 8 Issue: 1 Pages: 111-116
  • DOI: 10.3892/ol.2014.2138
  • Peer Reviewed / Open Access
• [Journal Article] Deflection of VEGF action by SS18-SSX and composite VEGF- and CXCR4-targeted therapy in synovial sarcoma. (2014)
  • Author(s): Wakamatsu T, Naka N, Sasagawa S, Tanaka T, Takenaka S, Araki N, Ueda T, Nishizawa Y, Yoshikawa H, Itoh K.
  • Journal Title: Cancer Sci. Volume: 105 Issue: 9 Pages: 1124-1134
  • DOI: 10.1111/cas.12469
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of a novel clear cell sarcoma cell line (Hewga-CCS), and investigation of the antitumor effects of pazopanib on Hewga-CCS. (2014)
  • Author(s): Outani H, Tanaka T, Wakamatsu T, Imura Y, Hamada K, Araki N, Itoh K, Yoshikawa H, Naka N.
  • Journal Title: BMC Cancer Volume: 14 Issue: 1 Pages: 455-455
  • DOI: 10.1186/1471-2407-14-455
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Combined targeting of mTOR and c-MET signaling pathways for effective management of epithelioid sarcoma. (2014)
  • Author(s): Imura Y, Yasui H, Outani H, Wakamatsu T, Hamada K, Nakai T, Yamada S, Myoui A, Araki N, Ueda T, Itoh K, Yoshikawa H, Naka N.
  • Journal Title: Mol Cancer Volume: 13 Issue: 1 Pages: 185-185
  • DOI: 10.1186/1476-4598-13-185
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tailored therapeutic strategies for synovial sarcoma: Receptor tyrosine kinase pathway analyses predict sensitivity to the mTOR inhibitor RAD001. (2014)
  • Author(s): Yasui H, Naka N, Imura Y, Outani H, Kaneko K, Hamada K, Sasagawa S, Araki N, Ueda T, Itoh K, Myoui A, Yoshikawa H.
  • Journal Title: Cancer Lett. Volume: 347 Pages: 114-122
  • Peer Reviewed
• [Journal Article] A novel angiomatoid epithelioid sarcoma cell line, Asra-EPS, forming tumors with large cysts containing hemorrhagic fluid in vivo. (2013)
  • Author(s): Imura Y, Naka N, Outani H, Yasui H, Takenaka S, Hamada K, Ozaki R, Kaya M, Yoshida K, Morii E, Myoui A, Yoshikawa H.
  • Journal Title: BMC Res Notes. Volume: 6 Pages: 305-305
  • Peer Reviewed
• [Journal Article] Dynamic analysis of lung metastasis by mouse osteosarcoma LM8: VEGF is a candidate for anti-metastasis therapy. (2013)
  • Author(s): Tanaka T, Yui Y, Naka N, Wakamatsu T, Yoshioka K, Araki N, Yoshikawa H, Itoh K.
  • Journal Title: Clin Exp Metastasis. Volume: 30 Pages: 369-379
  • Peer Reviewed
• [Presentation] 類上皮肉腫に対するmTORとc-METを標的とした抗腫瘍効果 (2014)
  • Author(s): 伊村慶紀，王谷英達，濱田健一郎，名井 陽，中 紀文，吉川秀樹
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
  • Invited
• [Presentation] 肉腫と幹細胞 (2014)
  • Author(s): 中 紀文
  • Organizer: 第47回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-17 – 2014-07-18
  • Invited
• [Presentation] 類上皮肉腫に対するmTOR阻害剤(RAD001)とMET阻害剤(INC280)の併用による抗腫瘍効果 (2014)
  • Author(s): 伊村慶紀，安井広彦，王谷英達，濱田健一郎，竹中 聡，名井 陽，中 紀文，吉川秀樹
  • Organizer: 第47回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] 滑膜肉腫へのmTOR阻害剤の効果を予測するバイオマーカーの提案 (2014)
  • Author(s): 安井広彦，伊村慶紀，王谷英達，濱田健一郎，竹中 聡，名井 陽，中 紀文，吉川秀樹
  • Organizer: 第47回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] Combined targeting of mTOR and c-MET significantly inhibits epithelioid sarcoma cell growth. (2014)
  • Author(s): Yoshinori Imura, Norifumi Naka, Hirohiko Yasui, Hidetatsu Otani, Keiko Kaneko, Satoshi Takenaka, Kenichiro Hamada, Satoru Sasagawa, Akira Myoui, Nobuhito Araki, Takafumi Ueda, Kazuyuki Itoh, Hideki Yoshikawa
  • Organizer: Metastasis research society 15th International Biennial Congress
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 2014-06-28 – 2014-07-01
• [Presentation] Dynamic analysis of lung metastasis by mouse osteosarcoma. (2014)
  • Author(s): Takaaki Tanaka, Yoshihiro Yui, Norifumi Naka, Toru Wakamatsu, Kazuyuki Itoh, Hideki Yoshikawa
  • Organizer: Metastasis research society 15th International Biennial Congress
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 2014-06-28 – 2014-07-01
• [Presentation] Antitumor effect of an mTOR inhibitor, RAD001 against epithelioid sarcoma cell lines (2013)
  • Author(s): Imura Y, Naka N, Outani H, Yasui H, Takenaka S, Hamada K, Myoui A, Yoshikawa H.
  • Organizer: International Society of Limb Salvage 17th General Meeting
  • Place of Presentation: Bologna, Italy
• [Presentation] Anti-tumor effect of an mTOR inhibitor, RAD001 to synovial sarcoma (2013)
  • Author(s): Yasui H, Naka N, Imura Y, Outani H, Kaneko K, Hamada K, Sasagawa S, Araki N, Ueda T, Itoh K, Myoui A, Yoshikawa H.
  • Organizer: International Society of Limb Salvage 17th General Meeting
  • Place of Presentation: Bologna, Italy
• [Presentation] Targeted strategy to treat synovial sarcomas (2013)
  • Author(s): Norifumi Naka
  • Organizer: 8th combined meeting of orthopaedic research societies
  • Place of Presentation: Venice, Italy
  • Invited
• [Presentation] 新規マウス軟部肉腫高肺転移株樹立の試み (2013)
  • Author(s): 金子恵子，王谷英達，中 紀文，吉川秀樹
  • Organizer: 第46回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 東京
• [Presentation] 新規淡明細胞肉腫株に対する抗血管新生阻害薬の治療効果 (2013)
  • Author(s): 王谷英達，中 紀文，伊村慶紀，安井広彦，吉川秀樹
  • Organizer: 第46回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 東京
• [Presentation] in vivoにて血腫形成を示す新規血管肉腫様類上皮肉腫細胞株の樹立 (2013)
  • Author(s): 伊村慶紀，中 紀文，王谷英達，吉川秀樹
  • Organizer: 第46回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 東京
• [Presentation] マウス骨肉腫細胞株Dunnと高肺転移亜株LM8における血中循環腫瘍細胞(CTCs)の動的・経時的解析 (2012)
  • Author(s): 田中太晶，伊藤和幸，中 紀文，吉川秀樹
  • Organizer: 第45回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 東京
• [Presentation] 骨・軟部腫瘍の分子標治療 (2012)
  • Author(s): 中 紀文
  • Organizer: 第85回日本整形外科学会学術集会
  • Place of Presentation: 京都
  • Invited