Identifying challenges to discover cancer stem-like cells in osteosarcoma

2013 Fiscal Year Final Research Report

• Project/Area Number: 23791629
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kanazawa University
• Principal Investigator: TAKEUCHI Akihiko 金沢大学, 大学病院, 助教 (70512218)
• Co-Investigator(Renkei-kenkyūsha): YAMAMOTO Yasuhiko 金沢大学, 医学系, 准教授 (20313637) ; MUNESUE Seiichi 金沢大学, 医学系, 助教 (10399040) ; HARASHIMA Ai 金沢大学, 脳・肝インターフェースメディシン研究センター, 助教 (50705522)
• Project Period (FY): 2011 – 2013
• Keywords: 骨・軟部腫瘍学

Research Abstract

Induced expression of RAGE (receptor for advanced glycation end-products) resulted in the co-expression of CD133 and CD24, stem-cell markers, in human osteosarcoma cell lines. Moreover, the RAGE-overexpressing cells showed higher spheroid-forming ability and a resistance to treatment of cisplatin, an anti-cancer drug, in vitro.Upregulated gene expression of cell-cycle and cell-division drivers was observed in microarray analyses . We also found that the expression of CD133 was significantly correlated with poor prognosis in patients with osteosarcoma using immunohistochemical analyses. Our results suggest that the RAGE could elicit the expression of cancer stem cell markers and may promote the cancer stem-like cell characteristics in osteosarcoma.

Research Products

• [Journal Article] Prognostic value of histological response to chemotherapy in osteosarcoma patients receiving tumor-bearing frozen autograft (2013)
  • Author(s): Miwa S, Takeuchi A, Ikeda H, Shirai T, Yamamoto N, Nishida H, Hayashi K, Tanzawa Y, Kimura H, Igarashi K, Tsuchiya H
  • Journal Title: PLoS One Volume: 8 Pages: e71362
  • DOI: 10.1371/journal.pone.0071362
  • Peer Reviewed
• [Journal Article] Prognostic value of radiological response to chemotherapy in patients with osteosarcoma (2013)
  • Author(s): Miwa S, Takeuchi A, Shirai T, Taki J, Yamamoto N, Nishida H, Hayashi K, Tanzawa Y, Kimura H, Igarashi K, Ooi A, Tsuchiya H
  • Journal Title: PLoS One Volume: 8 Pages: e70015
  • DOI: 10.1371/journal.pone.0070015
  • Peer Reviewed
• [Journal Article] H. Complete necrosis of a giant cell tumor with high expression of PPARγ : a case report (2013)
  • Author(s): Takeuchi A, Yamamoto N, Nishida H, Kimura H, Ikeda H, Tsuchiya H
  • Journal Title: Anticancer Res Volume: 33 Pages: 2169-74
  • URL: http://ar.iiarjournals.org/content/33/5/2169
  • Peer Reviewed
• [Journal Article] Low molecular weight heparin suppresses receptor for advanced glycation end products-mediated expression of malignant phenotype in human fibrosarcoma cells (2013)
  • Author(s): Takeuchi A, Yamamoto Y, Munesue S, Harashima A, Watanabe T, Yonekura H, Yamamoto H, Tsuchiya H
  • Journal Title: Cancer Sci Volume: 104 Pages: 740-9
  • DOI: 10.1111/cas.12133
  • Peer Reviewed
• [Journal Article] Uncultured adipose-derived regenerative cells promote peripheral nerve regeneration (2013)
  • Author(s): Suganuma S, Tada K, Hayashi K, Takeuchi A, Sugimoto N, Ikeda K, Tsuchiya H
  • Journal Title: J Orthop Sci Volume: 18 Pages: 145-51
  • DOI: 10.1007/s00776-012-0306-9
  • Peer Reviewed
• [Journal Article] Over 10-year follow-up of functional outcome in patients with bone tumors reconstructed using distraction osteogenesis (2013)
  • Author(s): Watanabe K, Tsuchiya H, Yamamoto N, Shirai T, Nishida H, Hayashi K, Takeuchi A, Matsubara H, Nomura I
  • Journal Title: J Orthop Sci Volume: 18 Pages: 101-9
  • DOI: 10.1007/s00776-012-0327-4
  • Peer Reviewed
• [Journal Article] Fifteen-year survivor of renal cell carcinoma after metastasectomies for multiple bone metastases (2013)
  • Author(s): Kato S, Murakami H, Takeuchi A, Demura S, Yoshioka K, Kawahara N, Tomita K, Tsuchiya H
  • Journal Title: Orthopedics Volume: 36 Pages: e1454-7
  • DOI: 10.3928/01477447-20131021-32
  • Peer Reviewed
• [Journal Article] Treatment strategies for well-differentiated liposarcomas and therapeutic outcomes (2012)
  • Author(s): Yamamoto N, Hayashi K, Tanzawa Y, Kimura H, Takeuchi A, Igarashi K, Inatani H, Shimozaki S, Kitamura S, Tsuchiya H
  • Journal Title: Anticancer Res Volume: 32 Pages: 1821-5
  • URL: http://ar.iiarjournals.org/content/32/5/1821
  • Peer Reviewed
• [Journal Article] A novel combined radiological method for evaluation of the response to chemotherapy for primary bone sarcoma (2012)
  • Author(s): Miwa S, Taki J, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y, Kimura H, Takeuchi A, Igarashi K, Ooi A, Tsuchiya H
  • Journal Title: J Surg Oncol Volume: 106 Pages: 273-9
  • DOI: 10.1002/jso.23074
  • Peer Reviewed
• [Journal Article] Caffeine induces apoptosis of osteosarcoma cells by inhibiting AKT/mTOR/S6K, NF-κB and MAPK pathways (2012)
  • Author(s): Miwa S, Sugimoto N, Yamamoto N, Shirai T, Nishida H, Hayashi K, Kimura H, Takeuchi A, Igarashi K, Yachie A, Tsuchiya H
  • Journal Title: Anticancer Res Volume: 32 Pages: 3643-9
  • URL: http://ar.iiarjournals.org/content/32/9/3643
  • Peer Reviewed
• [Journal Article] TNF-αand tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors (2012)
  • Author(s): Miwa S, Nishida H, Tanzawa Y, Takata M, Takeuchi A, Yamamoto N, Shirai T, Hayashi K, Kimura H, Igarashi K, Mizukoshi E, Nakamoto Y, Kaneko S, Tsuchiya H
  • Journal Title: PLoS One Volume: 7 Pages: e52926
  • DOI: 10.1371/annotation/7c0f14e6-cfba-4f5f-b93d-1a149eaeec96
  • Peer Reviewed
• [Presentation] Zaltoprofenは骨巨細胞腫に対してPPARγ(peroxisome proliferator-activated receptorγ)の活性化により抗腫瘍効果および脂肪分化誘導を示す (2013)
  • Author(s): 武内章彦,山本憲男,西田英司,木村浩明,下崎真吾,加藤貴士,山本靖彦,土屋弘行
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20131026-27
• [Presentation] 骨肉腫に対するカフェイン併用化学療法と縮小手術の中長期成績 (2013)
  • Author(s): 武内章彦,山本憲男,白井寿治,西田英司,林克洋,丹沢義一,木村浩明,五十嵐健太郎,稲谷弘幸,下崎真吾,加藤貴士,青木裕,土屋弘行
  • Organizer: 第51回日本癌治療学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 20131024-26
• [Presentation] 低分子ヘパリンは線維肉腫細胞における後期糖化産物受容体(RAGE)を介する悪性度を抑制する (2013)
  • Author(s): 武内章彦,山本靖彦,棟居聖一,原島愛,山本憲男,土屋弘行
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 20131003-05
• [Presentation] 骨巨細胞腫に対するペルオキシゾーム増殖剤応答性受容体ガンマ活性化による分化誘導及び抗腫瘍効果の解析 (2013)
  • Author(s): 武内章彦,山本憲男,西田英司,木村浩明,五十嵐健太郎,下崎真吾,加藤貴士,田中一広,山本靖彦,土屋弘行
  • Organizer: 第46回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 東京ドームホテル
  • Year and Date: 20130711-12
• [Presentation] 粘液型脂肪肉腫におけるペルオキシゾーム増殖剤応答性受容体ガンマの発現と臨床経過との相関 (2013)
  • Author(s): 武内章彦,山本憲男,西田英司,木村浩明,五十嵐健太郎,下崎真吾,加藤貴士,土屋弘行
  • Organizer: 第46回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 東京ドームホテル
  • Year and Date: 20130711-12
• [Presentation] 骨肉腫に対するカフェイン併用化学療法と縮小手術 (2013)
  • Author(s): 武内章彦,山本憲男,白井寿治,林克洋,西田英司,丹澤義一,木村浩明,三輪真嗣,土屋弘行
  • Organizer: 第86回日本整形外科学会学術集会
  • Place of Presentation: リーガロイヤルホテル広島
  • Year and Date: 20130523-26
• [Presentation] 骨肉腫におけるがん幹細胞研究 (2012)
  • Author(s): 武内章彦,山本靖彦,山本博,土屋弘行
  • Organizer: 第45回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 20120714-15
• [Patent(Industrial Property Rights)] 骨・軟部に発生する巨細胞性腫瘍または軟骨肉腫の予防または治療のための薬剤、動脈塞栓術用局所注入材、および人工骨 (2013)
  • Inventor(s): 武内章彦、土屋弘行
  • Industrial Property Rights Holder: 武内章彦、土屋弘行
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2013-199076
  • Filing Date: 2013-09-25
• [Patent(Industrial Property Rights)] 骨・軟部に発生する巨細胞性腫瘍の予防または治療剤 (2013)
  • Inventor(s): 武内章彦、土屋弘行
  • Industrial Property Rights Holder: 金沢大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: PCT/JP2013/0587706
  • Filing Date: 2013-03-18
  • Overseas
• [Patent(Industrial Property Rights)] 骨・軟部に発生する巨細胞性腫瘍の予防または治療剤 (2012)
  • Inventor(s): 武内章彦、土屋弘行
  • Industrial Property Rights Holder: 金沢大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2012-235784
  • Filing Date: 2012-10-25