Role of Epithelial-Mesenchymal Transition in Oral Cancer

• Project/Area Number: 20592135
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KATSUBE Kenichi Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 講師 (20233760)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腫瘍 / 上皮-間葉転換 / 口腔癌 / 上皮-間葉移行 / 扁平上皮癌 / 腎癌 / MMP / snail / 上皮問葉移行 / RANKL / amelogenin / 歯原性腫瘍

Research Abstract

In this study, we focused on the two different tumors. One is renal cell carcinoma (RCC), which has been well studied from the aspect of molecular signal of epithelial mesenchymal transition. The other is the common oral tumors; keratocystic odontogenic tumor and oral squamous cell carcinoma. In RCC, we focused on the role of RANKL, which was recently reported to be directly involved in tumor invasion, other than the induction of osteoclastogenesis in bone metastasis. From our Clinicopathological study, high invasive RACC such as the clear cell type has high level expression of RANKL. In vitro study using RCC cell line such as Kaki shoed that the introduction of RANKL gene increased the high mobility in vitro and high invasiveness in transplant study. We are investigating the role of other factors such as MMP and snail transcriptional factor. In keratocystic odontogenic tumor (KCOT), we screened the cytokeratin expression change. Among the keratin proteins, Cytokeratin 17 and 19 has been dramatically upregulated in KCOT, not in orthokeratinized odontogenic cyst (non-tumor type cyst). In squamous cell carcinoma, Cytokeratin 4 and 13 showed the distinct expression pattern and this change is also observed in the epithelial dysplasia. These changes is indicated to reciprocally relate to the Notch gene expression and in vitro transfection study of these keratin genes is ongoing.

Research Products

• [Journal Article] Downregulation of keratin 4 and keratin 13 expression in oral squamous cell carcinoma and epithelial dysplasia : a clue for the histopathogenesis (2011)
  • Author(s): Sakamoto K, Aragaki T, Morita K, Kawachi H, Kayamori K, Nakanishi S, Omura K, Miki Y, Okada N, Katsube K, Takizawa T, Yamaguchi A
  • Journal Title: Histopathology in press
• [Journal Article] Down-regulation of keratin 4 and keratin 13 expression in oral squamous cell carcinoma and epithelial dysplasia : a due for histopathogenesis. (2011)
  • Author(s): Sakamoto K, Aragaki T, Morita K, Kawachi H, Kayamori K, Nakanishi S, Omura K, Miki Y, Okada N, Katsube K, Takizawa T, Yamaguchi A.
  • Journal Title: Histopathology Volume: 58 Pages: 531-542
  • Peer Reviewed
• [Journal Article] Comprehensive keratin profiling reveals different histopathogenesis of keratocystic odontogenic tumor and orthokeratinized odontogenic cyst (2010)
  • Author(s): Aragaki T, Sakamoto K, Michi Y, Katsube K, Uzawa N, Okada N, Akashi T, Amagasa T, Yamaguchi A
  • Journal Title: Human Pathology 41(12) Pages: 1718-1725
• [Journal Article] Osteogenic differentiation of mouse mesenchymal progenitor cell, Kusa-A1 is promoted by mammalian transcriptional repressor Rbpj. (2010)
  • Author(s): Wang S, Kawashima N, Sakamoto K, Katsube K, Umezawa A, Suda H
  • Journal Title: Biochem Biophys Res Commun. 400(1)(Epub 2010 Aug 4) Pages: 39-45
• [Journal Article] Comprehensive keratin profiling reveals different histopathogenesis of keratocystic odontogenictumor and orthokeratinized odontogenic cyst (2010)
  • Author(s): Aragaki T, Sakamoto K, Michi Y, Katsube K, 他4名
  • Journal Title: Human Pathology Volume: 41 Pages: 1718-1725
  • Peer Reviewed
• [Journal Article] Periostin associates with Notch1 precursor to maintain Notch1 expression under a stress condition in mouse cells. (2010)
  • Author(s): Tanabe H, Takayama I, Nishiyama T, Shimazaki M, Kii I, Li M, Amizuka N, Katsube K, Kudo A.
  • Journal Title: Plos One Volume: 18
  • Peer Reviewed
• [Journal Article] CCN3 and bone marrow cells (2009)
  • Author(s): Katsube K, Ichikawa S, Katsuki Y, Kihara T, Terai M.Tamura Y, Lau LF, Takeda S, Umezawa A,Sakamoto K, Yamaguchi A.
  • Journal Title: Journal of Cell Communication and Signalling. 3(2) Pages: 135-145
• [Journal Article] Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas. (2009)
  • Author(s): Mikami S, Katsube K, Oya M, Ishida M, Kosaka T, Mizuno R, Mochizuki S, Ikeda T, Mukai M, Okada Y.
  • Journal Title: Journal of Pathology. 218(4) Pages: 530-539
• [Journal Article] Early serial Q-switched ruby laser therapy for medium-sized to giant congenital melanocytic naevi. (2009)
  • Author(s): Kishi K, Okabe K, Ninomiya R, Konno E, Hattori N, Katsube K, Imanish N, Nakajima H, Nakajima T.
  • Journal Title: British Journal of Dermatology. 161(2) Pages: 345-352
• [Journal Article] Treatment of giant congenital melanocytic nevi with enzymatically separated epidermal sheet grafting. (2009)
  • Author(s): Kishi K, Ninomiya R, Okabe K, Konno E, Katsube K, Imanishi N, Nakajima H, Nakajima T.
  • Journal Title: Journal of Plastic, Reconstructive & Aesthetic Surgery.
• [Journal Article] Transition of Cleaved Notch1 and Gene Expression Changes in Myeloblastic Leukemia Cells Stimulated with Notch Ligands (2009)
  • Author(s): Fu L, Katsube K, Tohda S
  • Journal Title: Anticancer Research 10 Pages: 3967-3970
  • Peer Reviewed
• [Journal Article] CCN3 and bone marrow cells. (2009)
  • Author(s): Katsube K, Ichikawa S, Katsuki Y, Kihara T, Terai M, Lau LF, Tamamura Y, Takeda S, Umezawa A, Sakamoto K, Yamaguchi A
  • Journal Title: J Cell Commun Signal. 2 Pages: 135-145
  • Peer Reviewed
• [Journal Article] Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas. (2009)
  • Author(s): Mikami S, Katsube K, Oya M, Ishida M, Kosaka T, Mizuno R, Mochizuki S, Ikeda T, Mukai M, Okada Y.
  • Journal Title: J Pathol 218 Pages: 530-539
  • Peer Reviewed
• [Journal Article] CCN, a vertebrate specific gene family and Development (2009)
  • Author(s): Ka tsube K, Sakamoto R, Y, Tamamura, Akira Yamaguchi
  • Journal Title: Development, Growth and Different iat ion 51 Pages: 55-67
  • Peer Reviewed
• [Journal Article] E-cadherin expression in the subepithelial nevus cells of the giant congenital nevocellular nevi (GCNN) correlates with their migration ability in vitro. (2008)
  • Author(s): Matsuda N, Katsube K, Mikami S, Katsuki Y, Iseki H, Mukai M, Yamaguchi A, Takano Y, Nakajima T, Nakajima H, Kishi K
  • Journal Title: Journal of Dermatological Science 52(1) Pages: 21-30
• [Journal Article] Zfp64 participates in Notch signaling and regulates differentiation in mesenchymal cells. (2008)
  • Author(s): Sakamoto K, Tamamura Y, Katsube K, Yamaguchi A
  • Journal Title: Journal of Cell Science 121(10) Pages: 1613-1623
• [Journal Article] Amelogenin positive cells scattered in the interstitial component of odontogenic fibromas. (2008)
  • Author(s): Kabasawa Y, Nagumo K, Takeda Y, Kawashima N, Okada N, Omura Ken, Yamaguchi A, Katsube K
  • Journal Title: Journal of Clinical Pathology 61(7) Pages: 851-855
• [Journal Article] Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1. (2008)
  • Author(s): Katsuki Y, Sakamoto K, Minamizato T, Makino H, Umezawa A, Ikeda MA, Perbal B, Amagasa T, Yamaguchi A, Katsube K
  • Journal Title: Biochemical and Biophysical Research Communications 368(3) Pages: 808-814
• [Journal Article] E-cadher in expression in the subepi the1ia1 nevus cells ofthe giant congenital nevocellular nevi (GCNN)correlateswith the ir migration ability in vitro (2008)
  • Author(s): Matsuda N, Katsube K, Mikami S, Katsuki Y, IsekiH, Mukai M, Yamaguchi A, Takano Y, Nakaj ima T, Nakaj iia H, Kishi K
  • Journal Title: Journal of Dermatological Science 52 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Zfp64 participates in Notch signaling and regulates differentiation in mesenchymal cells (2008)
  • Author(s): Sakamoto K, Tamamura Y, Katsube K, Yamaguchi A
  • Journal Title: Journal of Cell Science 121 Pages: 1613-1623
  • Peer Reviewed
• [Journal Article] Periostin associates with Notch1 precursor to maintain Notch1 expression under a stress condition in mouse cells.
  • Author(s): Tanabe H, Takayama I, Nishiyama T, Shimazaki M, Kii I, Li M, Amizuka N, Katsube K, Kudo A
  • Journal Title: Plos One 5(8)
• [Journal Article] Transition of Cleaved Notch1 and Gene Expression Changes in Myeloblastic Leukemia Cells Stimulated with Notch Ligands
  • Author(s): Fu L, Katsube K, Tohda S
  • Journal Title: Anticancer Research (Epub 2009 Jun 24) Pages: 917623-917623
• [Presentation] CCNファミリーによる間葉系分化シグナル調節 (2010)
  • Author(s): 勝部憲一
  • Organizer: 日本発生生物学会
  • Place of Presentation: 京都
  • Year and Date: 2010-06-23
• [Presentation] CCN3・Notchシグナルの骨形成に措ける役割 (2010)
  • Author(s): 勝部憲一
  • Organizer: 日本発生生物学会・環太平洋発生物学会合同年会
  • Place of Presentation: 京都
• [Presentation] CCN3の発生・再生における機能 (2009)
  • Author(s): 勝部憲一
  • Organizer: 日本CCN研究会
  • Place of Presentation: 岡山
  • Year and Date: 2009-08-30
• [Presentation] 骨形成・骨再生におけるCCN3の役割 特別講演 (2009)
  • Author(s): 勝部憲一
  • Organizer: 第3回日本CCN研究会
  • Place of Presentation: 岡山
• [Presentation] 歯原性線維腫におけるアメロジェニン陽性細胞の役割 (2008)
  • Author(s): 勝部 憲一
  • Organizer: 日本口腔科学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2008-04-17
• [Presentation] 歯原性線維腫におけるアメロジェニン陽性細胞の役割 (2008)
  • Organizer: 第62回日本口腔科学会学術集会 ミニシンポジウム 歯原性腫瘍の治療科学
  • Place of Presentation: 福岡
• [Presentation] CCCN3 and Notch/BMP Signals(口演) (2008)
  • Author(s): 勝部憲一
  • Organizer: 第5回CCN遺伝子ファミリー国際会議
  • Place of Presentation: Toronto、カナダ
• [Remarks]
  • URL: http://www.tmd.ac.jp/dent/opat/katsube.files/katsubel.html
• [Remarks]
  • URL: http://www.tmd.ac.jp/dent/opat/katsube.files/katsubel.html