Elucidation of mechanism of BMP signaling in bone invasion by oral squamous cell carcinoma cells

• Project/Area Number: 22791795
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Saitama Medical University
• Principal Investigator: SHIN Masashi 埼玉医科大学, 医学部, 研究員 (70549261)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 口腔癌 / シグナル伝達 / 骨

Research Abstract

Cancer cells in the oral cavity frequently invade alveolar bone. Although bone invasion by oral carcinoma cells is a critical factor for determination of prognosis, molecular mechanisms are unclear because an animal model in vivo of this event has not been established yet. In the present study, we examined roles of BMP signaling in bone invasion by cancer cells in vivo and in vitro. Over-expression of a constitutively active BMP receptor in vitro induced morphological changes. A cell line stably expressing a constitutively active BMP receptor, but not an empty vector, showed bone invasion in vivo. These findings suggest that BMP signaling stimulates bone invasion by cancer cells.

Research Products

• [Journal Article] Selective inhibition of NF-κB suppresses bone invasion by oral squamouscell carcinoma in vivo (2012)
  • Author(s): Furuta H, Osawa K, Shin M, Ishikawa A, Matsuo K, Khan M, AokiK, Ohya K, Okamoto M, Tominaga K, TakahashiT, Nakanishi O, Jimi E
  • Journal Title: Int J Cancer Volume: (in press)
  • Peer Reviewed
• [Journal Article] Identification and functional analysis of Zranb 2 as a novel Smad-bindingprotein that suppresses BMP signaling (2012)
  • Author(s): Ohte S, Kokabu S, Iemura S, Sasanuma H, Yoneyama K, Shin M, Suzuki S, Fukuda T, Nakamura Y, Jimi E, NatsumeT, Katagiri T
  • Journal Title: J Cell Biochem Volume: 113 Pages: 808-814
  • Peer Reviewed
• [Journal Article] Selective inhibition of NF-kB suppresses bone invasion by oral squamous cell carcinoma in vivo (2012)
  • Author(s): Furuta H, Osawa K, Shin M, Ishikawa A, Matsuo K, Khan M, Aoki K, Ohya K, Okamoto M, Tominaga K, Takahashi T, Nakanishi O, Jimi E
  • Journal Title: International Journal of Cancer Volume: (in press) Issue: 5
  • DOI: 10.1002/ijc.27435
  • Peer Reviewed
• [Journal Article] Identification and functional analysis of Zranb2 as a novel Smad-binding protein that suppresses BMP signaling (2012)
  • Author(s): Ohte S
  • Journal Title: J Cell Biochem Volume: 113 Issue: 3 Pages: 808-814
  • DOI: 10.1002/jcb.23408
  • Peer Reviewed
• [Journal Article] The inhibition of RANKL/RANK signalingby osteoprotegerin suppresses boneinvasion by oral squamous cell carcinoma cells (2011)
  • Author(s): Shin M, Matsuo K, Tada T, FukushimaH, Furuta H, Ozeki S, Kadowaki T, YamamotoK, Okamoto M, Jimi E.
  • Journal Title: Carcinogenesis Volume: 32 Pages: 1634-1640
  • Peer Reviewed
• [Journal Article] A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H (2011)
  • Author(s): Ohte S, Shin M, Sasanuma H, Yoneyama K, Akita M, Ikebuchi K, Jimi E, Maruki Y, Matsuoka M, Namba A, Tomoda H, Okazaki Y, Ohtake A, Oda H, Owan I, Yoda T, Furuya H, Kamizono J, Kitoh H, Nakashima Y, Susami T, Haga N, Komori T, Katagiri T
  • Journal Title: Biochem Biophys Res Commun Volume: 407 Pages: 213-218
  • Peer Reviewed
• [Journal Article] Suppression of BMP-Smad signaling axis-induced osteoblastic differentiation by small C-terminaldomain phosphatase 1, a Smad phosphatase (2011)
  • Author(s): Kokabu S, Ohte S, Sasanuma H, Shin M, Yoneyama K, Murata E, Kanomata K, NojimaJ, Ono Y, Yoda T, Fukuda T, Katagiri T
  • Journal Title: Mol Endocrinol Volume: 25 Pages: 474-481
  • Peer Reviewed
• [Journal Article] The inhibition of RANKL/RANK signaling by osteoprotegerin suppresses bone in vasion by oral squamous cell carcinoma cells (2011)
  • Author(s): Shin M, et al
  • Journal Title: Carcinogenesis Volume: 32 Issue: 11 Pages: 1634-1640
  • DOI: 10.1093/carcin/bgr198
  • Peer Reviewed
• [Journal Article] A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H. (2011)
  • Author(s): Ohte S
  • Journal Title: Biochem Biophys Res Commun Volume: 407(1) Pages: 213-218
  • Peer Reviewed
• [Journal Article] Suppression of BMP-Smad signaling axis-induced osteoblastic differentiation by small C-terminal domain phosphatase 1, a Smad phosphatase. (2011)
  • Author(s): Kokabu S
  • Journal Title: Mol Endcrinol Volume: 25(3) Pages: 474-481
  • Peer Reviewed
• [Presentation] BMP初期応答遺伝子のIdファミリーにおけるBMP応答配列の同定 (2011)
  • Author(s): 進正史、古株彰一郎、自見英治郎、片桐岳信
  • Organizer: 第53回歯科基礎医学会学術大会
  • Place of Presentation: 岐阜
  • Year and Date: 2011-10-01
• [Presentation] BMP初期応答遺伝子のIdファミリーにおけるBMP応答配列の同定 (2011)
  • Author(s): 進正史
  • Organizer: 第53回歯科基礎医学会
  • Place of Presentation: 岐阜県岐阜市
  • Year and Date: 2011-10-01
• [Presentation] BMP Signaling Inhibits Myogenesis and Induces Osteoblastic Differentiation in Satellite Cells During Muscle Regeneration (2011)
  • Author(s): Katagiri T
  • Organizer: 2011 ASBMR Annual Meeting
  • Place of Presentation: サンディエゴ(アメリカ)
  • Year and Date: 2011-09-19
• [Presentation] BMP Type II Receptors Further Stimulate Constitutively Activated Mutant ALK2 found in Fibrodysplasia Ossiiicans Progressiva (2011)
  • Author(s): Ohte S
  • Organizer: 2011 ASBMR Annual Meeting
  • Place of Presentation: サンディエゴ(アメリカ)
  • Year and Date: 2011-09-19
• [Presentation] Identification of a Common BMP-responsive Element in the Id1, Id2 and Id3 Genes (2011)
  • Author(s): Masashi Shin, Satoshi Ohte, Katsumi Yoneyama, Hiroki Sasanuma, Shoichiro Kokabu, Toru Fukuda, Eijiro Jimi, Takenobu Katagiri
  • Organizer: 2011 ASBMR Annual Meeting
  • Place of Presentation: サンディエゴ(アメリカ)
  • Year and Date: 2011-09-17
• [Presentation] BMP初期応答遺伝子におけるBMP応答配列の解析 (2011)
  • Author(s): 進正史
  • Organizer: 第29回日本骨代謝学会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2011-07-30
• [Presentation] 進行性骨化性線維異形成症(FOP)で同定されたALK2変異体はII型BMP受容体によってさらに活性化される (2011)
  • Author(s): 大手聡
  • Organizer: 第29回日本骨代謝学会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2011-07-30
• [Presentation] 骨格筋の再生と異所性骨化におけるサテライト細胞に対するBMPシグナルの役割 (2011)
  • Author(s): 笹沼寛樹
  • Organizer: 第29回日本骨代謝学会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2011-07-28
• [Presentation] BMP signaling stimulates alveolar bone invasion by melanoma cells (2010)
  • Author(s): Masashi Shin, Hidefumi Fukushima, Hiroyuki Furuta, Kazuhiro Aoki, Masud Khan, Keiichi Ohya, Takenobu Katagiri, and Eijiro Jimi
  • Organizer: 16th International Conference of the INTERNATIONAL SOCIETY OF DIFFERENTIATION
  • Place of Presentation: 奈良
  • Year and Date: 2010-11-15
• [Presentation] BMP signaling stimulates alveolar bone invasion by melanoma cells (2010)
  • Author(s): Shin M
  • Organizer: 16^<th> International Conference of the INTERNATIONAL SOCIETY OF DIFFERENTIATION
  • Place of Presentation: 奈良
  • Year and Date: 2010-11-15
• [Presentation] SCP1はBMP誘導性の骨芽細胞分化においてSmadの下流因子を抑制する (2010)
  • Author(s): 進正史
  • Organizer: 第8回RCGMフロンティア国際シンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2010-11-03
• [Presentation] 骨芽細胞分化におけるBMPとWntシグナルの相互作用の解明 (2010)
  • Author(s): 笹沼寛樹
  • Organizer: 第8回RCGMフロンティア国際シンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2010-11-03
• [Presentation] 新規Smad結合因子Zranb2はBMPシグナル抑制因子である (2010)
  • Author(s): 大手聡
  • Organizer: 第8回RCGMフロンティア国際シンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2010-11-03
• [Presentation] Identification of Zranb2, a novel R-Smads binding protein, as a suppressor of BMP signaling. (2010)
  • Author(s): Ohte S
  • Organizer: 2010 ASBMR Annual Meeting
  • Place of Presentation: トロント(カナダ)
  • Year and Date: 2010-10-17
• [Presentation] Platelet Factor 4 is a novel potentiator of BMP-induced osteoblastic differentiation and bone formation. (2010)
  • Author(s): Katagiri T
  • Organizer: 2010 ASBMR Annual Meeting
  • Place of Presentation: トロント(カナダ)
  • Year and Date: 2010-10-17
• [Presentation] 口腔癌細胞の顎骨浸潤におけるBMPシグナル活性化の役割 (2010)
  • Author(s): 進正史、福島秀文、古田弘之、青木和広、マスードカーン、大谷啓一、片桐岳信、自見英治郎
  • Organizer: 第52回歯科基礎医学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-21
• [Presentation] 口腔扁平上皮癌の顎骨浸潤モデルにおけるNF-kBシグナルによる顎骨浸潤制御機構の解明 (2010)
  • Author(s): 古田弘之、進正史、福島秀文、自見英治郎
  • Organizer: 第52回歯科基礎医学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-21
• [Presentation] 口腔癌細胞の顎骨浸潤におけるBMPシグナル活性化の役割 (2010)
  • Author(s): 進正史
  • Organizer: 第52回歯科基礎医学会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-21
• [Presentation] 口腔扁平上皮癌の顎骨浸潤モデルにおけるNF-kBシグナルによる顎骨浸潤制御機構の解明 (2010)
  • Author(s): 古田弘之
  • Organizer: 第52回歯科基礎医学会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-21
• [Presentation] SmadホスファターゼによるBMP誘導性骨芽細胞分化の抑制機序 (2010)
  • Author(s): 片桐岳信
  • Organizer: 第52回歯科基礎医学会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-21
• [Presentation] PPM1A and SCP1, Smad phosphatases, inhibits BMP-induced osteoblastic differentiation by different molecular mechanisms (2010)
  • Author(s): Katagiri T
  • Organizer: 8^<th> International BMP Conference
  • Place of Presentation: ルーベン(ベルギー)
  • Year and Date: 2010-09-17
• [Presentation] Identification and characterization of a nuclear protein as a co-suppress or of BMP-regulated R-Smads (2010)
  • Author(s): Ohte S
  • Organizer: 8^<th> International BMP Conference
  • Place of Presentation: ルーベン(ベルギー)
  • Year and Date: 2010-09-15
• [Presentation] 血小板第4因子は血中の新規BMP活性促進因子である (2010)
  • Author(s): 片桐岳信
  • Organizer: 第28回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-22
• [Presentation] 新規R-Smad結合因子ZRANB2のBMPシグナル阻害活性 (2010)
  • Author(s): 大手聡
  • Organizer: 第28回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-21
• [Remarks]
  • URL: http://www.saitama-med.ac.jp/genome/Div04_PPhysiol/index.html
• [Remarks]
  • URL: http://www.saitama-raed.ac.jp/genome/Div04_PPhysiol/index.html
• [Remarks]
  • URL: http://www.saitama-med.ac.jp/genome/Div04_PPhysiol/index.html