Targeting of osteosarcoma and soft tissue sarcoma initiating cells

• Project/Area Number: 18390419
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kagoshima University
• Principal Investigator: KOMIYA Setsurou Kagoshima University, 大学院・医歯学総合研究科, 教授 (30178371)
• Co-Investigator(Kenkyū-buntansha): YOKOUCHI Masahiro 鹿児島大学, 大学院・医歯学総合研究科, 助教 (80359976) ; SETOGUCHI Takao 鹿児島大学, 医学部・歯学部附属病院, 助教 (40423727)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,030,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥2,730,000); Fiscal Year 2008: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2007: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2006: ¥6,200,000 (Direct Cost: ¥6,200,000)
• Keywords: 骨軟部肉腫 / がん幹細胞 / sarcoma-initiating cell / sarcoma-initiating cells / 骨肉腫

Research Abstract

細胞表面の抗原Xを用いて分離した細胞をヌードマウスに移植して腫瘍形成能力を比較検討したところ陽性細胞は陰性細胞と比較して有意に腫瘍形成能力が高かった。Real-time PCR を用いた解析で陽性細胞では陰性細胞と比較して未分化マーカー遺伝子の発現が有意に高かく、分化マーカーの発現が低かった。この細胞株は無血清培地では増殖しないがbFGF を添加することで抗原X 陽性細胞は維持されまたその割合も増加した。一方でCNTF を添加すると陽性細胞の比率が減少した。肉腫患者組織では正常組織と比較して抗原X の発現が亢進していた。この手法はがん幹細胞をターゲットとした軟部肉腫治療法の開発に有用であると考えられる。

Research Products

• [Journal Article] Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulation (2009)
  • Author(s): Motoyuki Tanaka^1, Takao Setoguchi1, Masataka Hirotsu, Hui Gao, Hiromi Sasaki, Yukihiro Matsunoshita, Setsuro Komiya
  • Journal Title: ^1These two authors contributed equally 100 Pages: 1957-65
  • Peer Reviewed
• [Journal Article] Stem cell factor prevents neuronal cell apoptosis after acute spinal cord injury (2009)
  • Author(s): Yamasaki K, Setoguchi T, Takenouchi T, Yone K, Komiya S
  • Journal Title: Spine 34(4) Pages: 323-7
  • NAID: 10027238493
  • Peer Reviewed
• [Journal Article] Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis (2009)
  • Author(s): Taniguchi N, Carames B, Ronfani L, Ulmer U, Komiya S, Bianchi ME, Lotz M
  • Journal Title: Proc Natl Acad Sci USA 106(4) Pages: 1181-6
  • Peer Reviewed
• [Journal Article] Activation of synoviolin promoter in rheumatoid synovial cells by a novel transcription complex of interleukin enhancer binding factor 3 and GA binding protein alpha (2009)
  • Author(s): Izumi T, Fujii R, Izumi T, Nakazawa M, Yagishita N, Tsuchimochi K, Yamano Y, Sato T, Fujita H, Aratani S, Araya N, Azakami K, Hasegawa D, Kasaoka S, Tsuruta R, Yokouti M, Ijiri K, Beppu M, Maruyama I, Nishioka K, Maekawa T, Komiya S, Nakajima T
  • Journal Title: Arthritis Rheum. 60(1) Pages: 63-72
  • Peer Reviewed
• [Journal Article] Expression of osterix inhibits bone morphogenetic protein-induced chondrogenic differentiation of mesenchymal progenitor cells (2009)
  • Author(s): Tominaga H, Maeda S, Miyoshi H, Miyazono K, Komiya S, Imamura T
  • Journal Title: J Bone Miner Metab. 27(1) Pages: 36-45
  • NAID: 10025336129
  • Peer Reviewed
• [Journal Article] Smurf2 induces ubiquitin-dependent degradation of Smurf1 to prevent migration of breast cancer cells (2009)
  • Author(s): Fukunaga E, Inoue Y, Komiya S, Horiguchi K, Goto K, Saitoh M, Miyazawa K, Koinuma D, Hanyu A, Imamura T
  • Journal Title: J Biol Chem. 283(51) Pages: 35660-7
  • Peer Reviewed
• [Journal Article] Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulation (2009)
  • Author(s): Motoyuki Tanaka, Takao Setoguchi
  • Journal Title: British Journal of Cancer (in press)
  • Peer Reviewed
• [Journal Article] CCAAT/enhancer-binding protein beta promotes osteoblast differentiation by enhancing Runx2 activity with ATF4. (2008)
  • Author(s): Tominaga H, Maeda S, Hayashi M, Takeda S, Akira S, Komiya S, Nakamura T, Akiyama H, Imamura T
  • Journal Title: Mol Biol Cell. 19(12) Pages: 5373-86
  • Peer Reviewed
• [Journal Article] Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis (2008)
  • Author(s): Hamada T, Torikai M, Kuwazuru A, Tanaka M, Horai N, Fukuda T, Yamada S, Nagayama S, Hashiguchi K, Sunahara N, Fukuzaki K, Nagata R, Komiya S, Maruyama I, Fukuda T, Abeyama K
  • Journal Title: Arthritis Rheum. 58(9) Pages: 2675-85
  • Peer Reviewed
• [Journal Article] Differential expression of GADD45beta in normal and osteoarthritic cartilage : potential role in homeostasis of articular chondrocytes (2008)
  • Author(s): Ijiri K, Zerbini LF, Peng H, Out HH, Tsuchimochi K, Otero M, Dragomir C, Walsh N, Bierbaum BE, Mattingly D, van Flandern G, Komiya S, Aigner T, Libermann TA, Goldring MB
  • Journal Title: Arthritis Rheum. 58(7) Pages: 2075-87
  • Peer Reviewed
• [Journal Article] Expression of apoptosis signal-regulating kinase 1 in mouse spinal cord under chronic mechanical compression : possible involvement of the stress-activated mitogen-activated protein kinase pathways in spinal cord cell apoptosis (2008)
  • Author(s): Takenouchi T, Setoguchi T, Yone K, Komiya S
  • Journal Title: Spine 33(18) Pages: 1943-50
  • Peer Reviewed
• [Journal Article] Stage-specific secretion of HMGB1 in cartilage regulates endochondral ossification (2007)
  • Author(s): Taniguchi N, Yoshida K, Ito T, Tsuda M, Mishima Y, Furumatsu T, Ronfani L, Abeyama K, Kawahara K, Komiya S, Maruyama I, Lotz M, Bianchi ME, Asahara H
  • Journal Title: Mol Cell Biol. 27(16) Pages: 5650-63
  • Peer Reviewed
• [Journal Article] HAS3-related hyaluronan enhances biological activities necessary for metastasis of osteosarcoma cells (2006)
  • Author(s): Tofuku K, Yokouchi M, Murayama T, Minami S, Komiya S
  • Journal Title: Int J Oncol. 29(1) Pages: 175-83
  • Peer Reviewed
• [Journal Article] Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage (2006)
  • Author(s): Sato T, Konomi K, Yamasaki S, Aratani S, Tsuchimochi K, Yokouchi M, Masuko-Hongo K, Yagishita N, Nakamura H, Komiya S, Beppu M, Aoki H, Nishioka K, Nakajima T
  • Journal Title: Arthritis Rheum. 54(3) Pages: 808-17
  • Peer Reviewed
• [Journal Article] Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells (2006)
  • Author(s): Shouda T, Hiraoka K, Komiya S, Hamada T, Zenmyo M, Iwasaki H, Isayama T, Fukushima N, Nagata K, Yoshimura A
  • Journal Title: Cancer Lett 231(2) Pages: 176-84
  • Peer Reviewed
• [Journal Article] がん幹細胞 (2006)
  • Author(s): 瀬戸口啓夫
  • Journal Title: 関節外科 26・2 Pages: 94-94
• [Journal Article] Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin (2006)
  • Author(s): Yamasaki S
  • Journal Title: ENBO JOURNAL 26・1 Pages: 113-122
• [Journal Article] Preventive effect of erythropoietin on spinal cord cell apoptosis following acute traumatic injury in rats. (2006)
  • Author(s): Arishima Y.
  • Journal Title: SPINE 31・21 Pages: 2432-2438
• [Journal Article] In vitro in vivo efficacy of a recombinant immunotoxin against folate receptor beta on the activation and proliferation of rheumatoid arthritis synovial cells. (2006)
  • Author(s): Nagai T.
  • Journal Title: Arthritis and rheumatism 54・10 Pages: 3126-34
• [Journal Article] In vitro in vivo efficacy of a recombinant immunotoxin against folate receptor beta on the activation and proliferation of rheumatoid arthritis synovial cells. (2006)
  • Author(s): Sato T.
  • Journal Title: Arthritis and rheumatism 54・3 Pages: 808-817
• [Journal Article] HAS3-related hyaluronan enhances biological activities necessary for metastasis of osteosarcoma cells. (2006)
  • Author(s): Tofuku K.
  • Journal Title: International journal of oncology 29・1 Pages: 175-183
• [Presentation] 骨・軟部腫瘍におけるがん幹細胞の研究 (2008)
  • Author(s): 瀬戸口啓夫、小宮節郎
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2008-10-24
• [Presentation] 骨・軟部腫瘍におけるがん幹細胞の研究 (2008)
  • Author(s): 瀬戸口啓夫, 小宮節郎, 他
  • Organizer: 第23回日本整形外科学会 基礎学術集会シンポディウム
  • Place of Presentation: 京都国際会議場(京都市)
  • Year and Date: 2008-10-24
• [Presentation] 骨軟部悪性腫瘍細胞株におけるがん幹細胞様細胞の研究 (2007)
  • Author(s): 瀬戸口啓夫、小宮節郎
  • Organizer: 第22回日本整形外科学会基礎学術集会
  • Place of Presentation: 静岡県 浜松市
• [Book] 関節外科 (2007)
  • Author(s): 瀬戸口啓夫 小宮節郎 近藤亨
  • Publisher: がん幹細胞と治療抵抗性