Metastasis suppression in head and neck squamous cell carcinoma by targeting DKK3 gene.

• Project/Area Number: 25861742
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Morphological basic dentistry
• Research Institution: Kawasaki Medical School
• Principal Investigator: Katase Naoki 川崎医科大学, 医学部, 助教 (30566071)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 頭頸部扁平上皮癌 / 扁平上皮癌 / DKK3 / がん抑制遺伝子 / 遺伝子機能解析 / 口腔扁平上皮癌 / Wnt signaling / 機能解析 / 細胞増殖 / 浸潤 / 転移 / 強制発現 / western blotting / Real time PCR / ELISA / Transfection

Outline of Final Research Achievements

In this research project, functional analyses on DKK3 gene were performed in head and neck squamous cell carcinoma (HNSCC). Although DKK3 is known as tumor suppressor of which expression is reduced in many kinds of malignancies, its expression is specifically high in HNSCC. In the present research, DKK3 overexpression (DKK3-OE) and DKK3 stable knockdown (DKK3-KD) were established, and detailed investigation was done on DKK3-OE model. DKK3-OE resulted in increased cellular proliferation, migration and invasion. Moreover, DKK3-OE cells showed increased tumor volume in nude mice xenograft model. To explain these results, influence of DKK3-OE on Wnt/β-catenin signal was investigated. However, TCF activity that will be increased by Wnt/β-catenin signal was not increased, although Wnt target gene expression was elevated. The results imply that DKK3 may exert oncogenic function via certain signal other than Wnt/β-catenin signal, specifically in HNSCC.

Research Products

• [Journal Article] Erratum to: miR-487b, miR-3963 and miR-6412 delay myogenic differentiation in mouse myoblast-derived C2C12 cells. (2016)
  • Author(s): Katase N, Terada K, Suzuki T, Nishimatsu S, Nohno T.
  • Journal Title: BMC Cell Biol. Volume: 17(1) Issue: 1
  • DOI: 10.1186/s12860-016-0083-y
  • Peer Reviewed / Open Access
• [Journal Article] A Case of Squamous Cell Carcinoma Arising from Branchial Cleft Cyst (2015)
  • Author(s): Nakano A., Mishima K., Katase N., Ueyama Y.
  • Journal Title: J Oral Maxillofac Surg Volume: 72 Issue: 4 Pages: 781-785
  • DOI: 10.1016/j.joms.2014.10.036
  • Peer Reviewed
• [Journal Article] miR-487b, miR-3963 and miR-6412 delay myogenic differentiation in mouse myoblast-derived C2C12 cells. (2015)
  • Author(s): Katase, N., Terada, K., Suzuki, T., Nishimatsu, S., and Nohno, T.
  • Journal Title: BMC Cell Biology Volume: 16 Issue: 1
  • DOI: 10.1186/s12860-015-0061-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Primary intraosseous squamous cell carcinoma of the maxilla possibly arising from an infected residual cyst: A case report. (2015)
  • Author(s): Sukegawa S, Matsuzaki H, Katase N, Kanno T, Mandai T, Takahashi Y, Asaumi J, Furuki Y
  • Journal Title: Oncol Lett. Volume: 9巻1号 Issue: 1 Pages: 131-135
  • DOI: 10.3892/ol.2014.2644
  • Peer Reviewed / Open Access
• [Journal Article] Expressions of ABCG2, CD133, and Podoplanin in Salivary Adenoid Cystic Carcinoma. (2014)
  • Author(s): Li W, Tamamura R, Wang B, Liu Q, Liu H, Liu T, Katase N, Xiao J, Nagatsuka H.
  • Journal Title: Biomed Res Int. Volume: 2014 Pages: 1-11
  • DOI: 10.1155/2014/132349
  • Peer Reviewed / Open Access
• [Journal Article] Expression and roles of CCN2 in dental mesenchymal cells in primary culture-With findings in a case of odontogenic myxofibroma. (2014)
  • Author(s): Shimo T, Koyama E, Horikiri Y, Okui T, Kurio N, Katase N, Yoshida S, Takebe Y, Kishimoto K, Yoshioka N, Nagatsuka H, Sasaki A
  • Journal Title: Oral Sci Int. Volume: 11巻1号 Issue: 1 Pages: 8-14
  • DOI: 10.1016/s1348-8643(13)00008-6
  • Peer Reviewed / Open Access
• [Journal Article] Fibrous dysplasia of the maxilla: a case report together with its conventional imaging and dynamic magnetic resonance imaging findings. (2014)
  • Author(s): Hara M, Matsuzaki H, Katase N, Unetsubo T, Yanagi Y, Nagatsuka H, Asaumi J.
  • Journal Title: Oral Radiol. Volume: 30巻1号 Issue: 1 Pages: 105-110
  • DOI: 10.1007/s11282-013-0137-1
  • Peer Reviewed
• [Journal Article] Knockdown of Dkk-3 decreases cancer cell migration and invasion independently of the Wnt pathways in oral squamous cell carcinoma‑derived cells. (2013)
  • Author(s): Katase N
  • Journal Title: Oncol Rep. Volume: 29 Issue: 4 Pages: 1349-1355
  • DOI: 10.3892/or.2013.2251
  • Peer Reviewed
• [Journal Article] Epithelium-poor type Central Odontogenic Fibroma: An Immunohistological Study and Review of the Literature. (2013)
  • Author(s): Kimura T, Ohba S, Yoshimura H, Katase N, Imamura Y, Ueno T, Nagatsuka H, Sano K
  • Journal Title: J Hard Tissue Biol. Volume: 22巻2号 Pages: 273-278
  • NAID: 130004480591
  • Peer Reviewed
• [Journal Article] DKK3 (dickkopf 3 homolog (Xenopus laevis)) (2013)
  • Author(s): Katase N, Nohno T
  • Journal Title: Atlas Genet Cytogenet Oncol Haematol. Volume: -
  • Peer Reviewed
• [Journal Article] Diagnostic value of MRI for odontogenic tumours. (2013)
  • Author(s): Fujita M, Matsuzaki H, Yanagi Y, Hara M, Katase N, Hisatomi M, Unetsubo T, Konouchi H, Nagatsuka H, Asaumi JI.
  • Journal Title: Dentomaxillofac Radiol. Volume: 42巻5号 Issue: 5 Pages: 20120265-20120265
  • DOI: 10.1259/dmfr.20120265
  • Peer Reviewed
• [Journal Article] Improvement of the Efficacy of 5-aminolevulinic Acid-mediated Photodynamic Treatment in Human Oral Squamous Cell Carcinoma HSC-4. (2013)
  • Author(s): Yamamoto M, Fujita H, Katase N, Inoue K, Nagatsuka H, Utsumi K, Sasaki J, Ohuchi H
  • Journal Title: Acta Med Okayama. Volume: 67巻3号 Pages: 153-164
  • NAID: 120005295913
  • Peer Reviewed
• [Journal Article] Interaction of Wnt signaling with BMP/Smad signaling during the transition from cell proliferation to myogenic differentiation in mouse myoblast-derived cells (2013)
  • Author(s): Terada K,Misao S,Katase N,Nishimatsu S,Nohno T
  • Journal Title: Int J Cell Biol 2013 Volume: (Article ID 616294) Pages: 1-11
  • DOI: 10.1155/2013/616294
  • Peer Reviewed
• [Journal Article] The Ability of Transplanted Bone Marrow-Derived Cells to Differentiate into Parenchymal Cells of Salivary Glands. (2013)
  • Author(s): Yuan YW, Tamamura R, Lei L, Katase N, Sathi GA, Ito S, Tsujigiwa H, Nagatsuka H.
  • Journal Title: J Hard Tissue Biol. Volume: 22巻4号 Pages: 433-438
  • NAID: 130004480613
  • Peer Reviewed
• [Journal Article] Swelling of the floor of the mouth in an infant. (2013)
  • Author(s): Matsuzaki H, Katase N, Moritani N, Hara M, Yanagi Y, Asaumi JI.
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Volume: 116巻4号 Issue: 4 Pages: 392-397
  • DOI: 10.1016/j.oooo.2012.03.025
  • Peer Reviewed
• [Journal Article] Establishment of odontoblastic cells, which indicate odontoblast features both in vivo and in vitro (2013)
  • Author(s): Tsujigiwa H, Katase N, Lefeuvre M, Yamachika E, Tamamura R, Ito S, Takebe Y, Matsuda H, Nagatsuka H
  • Journal Title: J Oral Pathol Med Volume: 42(10) Issue: 10 Pages: 799-806
  • DOI: 10.1111/jop.12080
  • Peer Reviewed
• [Presentation] 口腔癌由来細胞におけるDKK3遺伝子発現の影響 (2015)
  • Author(s): 片瀬 直樹, 寺田 久美子, 西松 伸一郎, 鈴木 貴弘, 松崎 秀紀, 山村 真弘, 山内 明，大槻 剛巳, 濃野 勉
  • Organizer: 第38回 日本分子生物学会年会 第88回 日本生化学会大会 合同大会
  • Place of Presentation: 神戸市 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] Functional analyses of DKK3 in oral squamous cell carcinoma cell lines 口腔癌由来細胞株におけるDKK3遺伝子の機能解析 (2015)
  • Author(s): Katase N, Yamamura M, Yamauchi A, Nishimatsu S, Nohno T
  • Organizer: 第74回 日本癌学会学術総会
  • Place of Presentation: 名古屋市 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] HSP90 inhibitor inhibit the activation of multiple kinase pathways of pancreatic cancer cells (2015)
  • Author(s): Yamamura M, Yamauchi A, Katase N, Hirai T
  • Organizer: 第74回 日本癌学会学術総会
  • Place of Presentation: 名古屋市 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] 口腔扁平上皮癌におけるDKK3の発現と機能解析 (2015)
  • Author(s): 片瀬 直樹
  • Organizer: 第57回 歯科基礎医学会学術大会
  • Place of Presentation: 新潟市 朱鷺メッセ
  • Year and Date: 2015-09-11
• [Presentation] 腫瘍細胞におけるDKK3遺伝子強制発現／ノックダウンの影響 (2015)
  • Author(s): 片瀬 直樹
  • Organizer: 第6回 川崎医科大学学術集会
  • Place of Presentation: 倉敷市 川崎医科大学
  • Year and Date: 2015-08-01
• [Presentation] Knockdown of Dkk-3 decreases cancer cell migration and invasion independently of the Wnt pathways in oral squamous cell carcinoma‑derived cells. (2015)
  • Author(s): 片瀬 直樹
  • Organizer: 第26回 日本臨床口腔病理学会 総会・学術大会
  • Place of Presentation: 札幌市 北海道大学 学術交流会館
  • Year and Date: 2015-07-29
• [Presentation] Suppressing pancreatic cancer metastasis by small molecular compunds (2015)
  • Author(s): Yamauchi A, Yamamura M, Katase N, Itadani M, Okada N, Yamaguchi Y, Nohno T, Kuribayashi F
  • Organizer: がん免疫療法・マクロファージ 国際会議2015
  • Place of Presentation: 文京区 東京大学 伊藤国際 学術センター内 伊藤謝恩ホール
  • Year and Date: 2015-07-09
  • Int'l Joint Research
• [Presentation] 筋幹細胞特異的 Sema3A cKO マウスの解析 (2015)
  • Author(s): 鈴木 貴弘、西松 伸一郎、寺田 久美子、 片瀬 直樹、濃野 勉、水野谷 航、池内 義秀、 辰巳 隆一
  • Organizer: 第119回 日本畜産学会大会
  • Place of Presentation: 宇都宮大学（宇都宮市）
  • Year and Date: 2015-03-27 – 2015-03-30
• [Presentation] miR－487b、miR-3963はC2C12細胞の分化を 抑制する (2014)
  • Author(s): 寺田 久美子、片瀬 直樹、西松 伸一郎、濃野 勉
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] プロセシング酵素Furinによる骨格筋形成の制御 (2014)
  • Author(s): 西松 伸一郎、大澤 裕、寺田 久美子、片瀬 直樹、鈴木 貴弘、砂田 芳秀、濃野 勉
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] DKK3過剰発現が頭頸部扁平上皮癌細胞に及ぼす影響 (2014)
  • Author(s): 片瀬 直樹、西松 伸一郎、濃野 勉
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 食道がんにおける細胞増殖および遊走に対する HSP90阻害薬の効果 (2014)
  • Author(s): 山村 真弘、山内 明、岡田 尚子、片瀬 直樹、 刀祢 重信、岡脇 誠、澤木 明、栗林 太、濃野 勉、 山口 佳之
  • Organizer: 第25回日本消化器癌発生学会総会
  • Place of Presentation: ホテル日航福岡（福岡市）
  • Year and Date: 2014-11-13 – 2014-11-14
• [Presentation] Antitumor effect of HSP90 inhibitor against esophageal cancer 食道癌に対するHSP90阻害剤の抗腫瘍効果 (2014)
  • Author(s): Yamamura M, Hirai T, Nohno T, Katase N, Yamauchi A, Kuribayashi F, Okawaki M, Matsumoto H, Nakamura M, Yamaguchi Y.
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Dkk-3の頭頸部扁平上皮癌における発現の検討 (2014)
  • Author(s): 藤井 昌江、片瀬 直樹、高畠 清文、武部 祐一郎、 于 淞、河合 穂高、辻極 秀次、長塚 仁
  • Organizer: 第25回日本臨床口腔病理学会
  • Place of Presentation: メディアシップ 日報ホール（新潟市）
  • Year and Date: 2014-08-27 – 2014-08-29
• [Presentation] 頭頸部扁平上皮癌細胞におけるDKK3強制発現の影響 (2014)
  • Author(s): 片瀬 直樹
  • Organizer: 第25回日本臨床口腔病理学会
  • Place of Presentation: メディアシップ 日報ホール（新潟市）
  • Year and Date: 2014-08-27 – 2014-08-29
• [Presentation] DKK3をターゲットとした 頭頸部扁平上皮癌の転移抑制に関する研究 (2014)
  • Author(s): 片瀬 直樹
  • Organizer: 第5回川崎医科大学学術集会
  • Place of Presentation: 川崎医科大学（倉敷市）
  • Year and Date: 2014-08-02
• [Presentation] Exophiala dermatitidis 感染による肺出血および多発性脳梗塞を認めた急性骨髄性白血病の一剖検例 (2014)
  • Author(s): 伏見 聡一郎、伊藤 利洋、片瀬 直樹、玉村 亮、 サン タテ、板倉 淳哉、河原 明奈、小田 晋輔、 松川 昭博
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] エナメル上皮腫におけるCCN2の発現解析 (2014)
  • Author(s): 河合 穂高、武部 祐一郎、片瀬 直樹、于 淞、 藤井 昌江、高畠 清文、辻極 秀次、長塚 仁
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] DKK3 expression and its function in head and neck squamous cell carcinoma. (2014)
  • Author(s): Katase N, Gunduz M, Tsujigiwa H, Ito S, Fujii M, Nagatsuka H, Sasaki A, Nohno T
  • Organizer: AACR Annual Meeting 2014 San Diego
  • Place of Presentation: San Diego Convention Center (San Diego, USA)
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] 硬組織形成過程におけるハニカムβTCPを 用いた細胞内微小環境の検討
  • Author(s): 辻極 秀次, 伊藤 聡, 片瀬 直樹, 玉村 亮, 于 淞， 李 海テイ，武部 祐一郎, 河合 穂高, 長塚 仁
  • Organizer: 第67回日本口腔科学会
  • Place of Presentation: 栃木県総合文化センター（宇都宮）
• [Presentation] 腫瘍の微小環境形成に関与する骨髄由来細胞の動態について
  • Author(s): 玉村 亮, 武部 祐一郎, 片瀬 直樹, 河合 穂高, 辻極 秀次, 長塚 仁
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌（札幌市）
• [Presentation] 上顎残留嚢胞から発生したと考えられた原発性骨内扁平上皮癌の1例
  • Author(s): 助川 信太郎，管野 貴浩, 片瀬 直樹, 松崎 秀信, 高畑 和路, 高橋 由佳, 篠原 丈裕, 長塚 仁, 古木 良彦
  • Organizer: 第37回日本頭頸部癌学会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
• [Presentation] 頭頸部扁平上皮癌におけるDKK3発現と機能
  • Author(s): 片瀬 直樹, 濃野 勉
  • Organizer: 第86回日本生化学会
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] ハニカムβ-TCP細胞外微小環境下での 硬組織形成
  • Author(s): 伊藤 聡, 片瀬 直樹, 玉村 亮, 武部 祐一郎, 山近 英樹, 高木 慎, 長塚 仁
  • Organizer: 第58回日本口腔外科学会
  • Place of Presentation: 福岡国際会議場（福岡市）
• [Presentation] 頭頸部扁平上皮癌におけるDKK3の機能について
  • Author(s): 片瀬 直樹, 濃野 勉
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸国際会議場（神戸市）
• [Book] 病理と臨床 31巻5号 (2013)
  • Author(s): 長塚 仁, 片瀬 直樹
  • Total Pages: 6
  • Publisher: 文光堂
• [Book] Tumor Suppressor Genes: Functions, Regulation and Health Effects (2013)
  • Author(s): Katase N, Nohno T, Gunduz M
  • Total Pages: 25
  • Publisher: Nova Science Publisher