Elucidation of invasive andmetastatic mechanism in oral cancer for application to molecular based diagnosisand gene therapy

2012 Fiscal Year Final Research Report

• Project/Area Number: 21249088
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Hiroshima University
• Principal Investigator: TAKATA Takashi 広島大学, 大学院・医歯薬保健学研究院, 教授 (10154783)
• Co-Investigator(Kenkyū-buntansha): KUDO Yasusei 徳島大学, ヘルスバイオサイエンス研究部, 准教授 (50314753) ; SINDOH Masanobu 北海道大学, 大学院・歯学研究科, 教授 (20162802) ; HIDA Kyouko 北海道大学, 大学院・歯学研究科, 特任准教授 (40399952)
• Project Period (FY): 2009 – 2012
• Keywords: 口腔癌 / 浸潤・転移 / microRNA

Research Abstract

To elucidate invasive and metastatic mechanism in oral cancer for application to molecular based diagnosis and gene therapy, we conducted research in accordance with our projects. As a result, we identified Wnt5B and MMP10 as promoter of , microRNA-203 as suppressor of tumor invasion, Periostin as promoter of lymphangiogenesis, MMP-13 as promoter of angiogenesis. Additionally, we attempted to apply Periostin to Elisa for serum of oral cancer patients. Interestingly, we found upregulation of Periostin correlated with lymphonode metastasis status. Therefore, we showed Periostin could be a useful for molecular diagnostic marker in oral cancer.

Research Products

• [Journal Article] The 3D tissue microenvironment modulates DNA methylation and E-cadherin expression in squamous cell carcinoma (2012)
  • Author(s): Desrochers TM, Shamis Y, Alt-Holland A, Kudo Y, Takata T, Wang G, Jackson-Grusby L, Garlick JA.
  • Journal Title: Epigenetics Volume: 7(1) Pages: 34-46
  • Peer Reviewed
• [Journal Article] Nuclear Aurora B and cytoplasmic Survivin expression is involved in lymph node metastasis of colorectal cancer (2012)
  • Author(s): Tuncel H, Shimamoto F, Kaneko H, Aoki E, Jikihara H, Nakai S, Takata T, Tatsuka M
  • Journal Title: Oncology Let Volume: 3(5) Pages: 1109-1114
  • Peer Reviewed
• [Journal Article] Frequent increased gene copy number and high protein expression of tRNA (cytosine-5-)-methyltransferase (NSUN2) in human cancers. (2012)
  • Author(s): Okamoto M, Hirata S, Sato S, Koga S, Fujii M, Qi G, Ogawa I, Takata T, Shimamoto F, Tatsuka M
  • Journal Title: DNA Cell Biol Volume: 31(5) Pages: 660-71
  • Peer Reviewed
• [Journal Article] Periostin Directly and Indirectly Promotes Tumor Lymphangiogenesis of Head and Neck Cancer. (2012)
  • Author(s): Kudo Y, Iizuka S, Yoshida M, Nguyen PT, Siriwardena BSMS, Tsunematsu T, Ohbayashi M, Ando T, Hatakeyama D, Shibata T, Koizumi K, Maeda M, Ishimaru N, Ogawa I, Takata T
  • Journal Title: PLos ONE Volume: 7(8) Pages: e44488
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase-13(MMP-13) directly and indirectly promotes tumor angiogenesis. (2012)
  • Author(s): Kudo.Y, Iizuka.S, Yoshida.M, Tsunematsu.T, Kondo T, Subarnbhesaj A, Deraz EM, Siriwardena SB, Tahara H, Ishimaru N, Ogawa I,Takata T
  • Journal Title: J Biol Chem Volume: 287(46) Pages: 38716-28
  • Peer Reviewed
• [Journal Article] Prostacyclin receptor in tumor endothelial cells promotes angiogenesis in an autocrine manner (2012)
  • Author(s): Osawa T, Ohga N, Hida Y, Kitayama K, Akiyama K, Onodera Y, Fujie M, Shinohara N, Nonomura K, Shindoh M, Hida K
  • Journal Title: Cancer Sci Volume: 103(6) Pages: 1038-1044
• [Journal Article] Tumor-derived microvesicles induce proangiogenic phenotype in endothelial cells via endocytosis (2012)
  • Author(s): Kawamoto T, Ohga N, Akiyama K, Hirata N, Kitahara S, Maishi N., Osawa T., Yamamoto K., Kondoh M, Shindoh M, Hida Y, Hida K
  • Journal Title: PLoS ONE Volume: 7(3) Pages: e34045
• [Journal Article] Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells (2012)
  • Author(s): Yamamoto K, Ohga N, Hida Y, Maishi N, Kawamoto T, Kitayama K, Akiyama K, Osawa T, Kondoh M, Matsuda K, OnoderaY, Fujie M, Kaga K, Hirano S, Shinohara N, Shindoh M, Hida K
  • Journal Title: Br J Cancer Volume: 106 Pages: 1214-1223
• [Journal Article] CXCR7 : A novel tumor endothelial marker in renal cell carcinoma (2012)
  • Author(s): Maishi N, Ohga N, Hida Y, Akiyama K, Kitayama K, Osawa T, Onodera Y, Shinohara N, Nonomura K, Shindoh M, Hida K
  • Journal Title: Pathol Int Volume: 62(5) Pages: 309-317
• [Journal Article] Heterogeneity of Tumor Endothelial Cells: Comparison between Tumor Endothelial Cells Isolated from Highly Metastatic and Low Metastatic Tumors (2012)
  • Author(s): Ohga N, Ishikawa S, Maishi N, Akiyama K, Hida Y, Kawamoto T, Sadamoto Y, Osawa T,Yamamoto K,Kondoh M,Ohmura H,Shinohara N,Nonomura K,Shindoh M,Hida K
  • Journal Title: Am J Pathol Volume: 180(3) Pages: 1294-1307
• [Journal Article] Tumor endothelial cells acquire drug resistance by MDR1 upregulation via VEGF signaling in tumor microenvironment (2012)
  • Author(s): Akiyama K, Ohga N, Hida Y, Kawamoto T, Sadamoto Y., Ishikawa S, Maishi N, Akino T, Kondoh M, Matsuda A, Inoue N, Shindoh Mand Hida K
  • Journal Title: Am J Pathol Volume: 180(3) Pages: 1283-1293
• [Journal Article] MMP-10/stromelysin-2promotes invasion of head and neck cancer (2011)
  • Author(s): Deraz EM, Kudo Y, Yoshida M, Tani H, Tsunematsu, T, Siriwardena B.S.M.S, Kiekhaee MR, Qi G, Iizuka S, Ogawa, I, Campisi G, Lo Muzio L, Abiko Y, Kikuchi A, Takata T
  • Journal Title: PLoS ONE Volume: 6(10) Pages: e25438
  • Peer Reviewed
• [Journal Article] Incleased telomerase activity and hTERT expression in human salivary gland carcinomas (2011)
  • Author(s): Shigeishi H, Sugiyama M, Tahara H, Ono S, Bhawal UK, Okura M, Kogo M, Shinohara M, Shindoh M, Shintani S, Hamakawa H, Takata T, Kamata N
  • Journal Title: Oncology Letter Volume: 2 Pages: 845-850
  • Peer Reviewed
• [Journal Article] miR-22 represses cancer progression by inducing celular senescence (2011)
  • Author(s): Xu D, Takeshita F, Hino Y, Fukunaga S, Kudo Y, Tamaki A, Matsunaga J, Takahashi R, Takata T, Shimamoto A, Ochiya T, Tahara H
  • Journal Title: J Cell Biol Volume: 193(2) Pages: 409-24
  • Peer Reviewed
• [Journal Article] N-cadherin expression is involved in malignant behavior of head and neck cancer in relation to epithelial-mesenchymal transition (2011)
  • Author(s): Nguyen PT, Kudo Y, Yoshida M, Kamata N, Ogawa I, Takata T
  • Journal Title: Histol Histopathol Volume: 26(2) Pages: 147-56
  • Peer Reviewed
• [Journal Article] N-cadherin expression is correlated with metastasis of spindle cell carcinoma of head and neck region (2011)
  • Author(s): Nguyen PT, Kudo Y, Yoshida M, Iizuka S, Ogawa I, Takata T
  • Journal Title: J Oral PatholMed Volume: 40(1) Pages: 77-82
  • Peer Reviewed
• [Journal Article] Oncogenic role of RUNX3 in head and neck cancer (2011)
  • Author(s): Kudo Y, Tsunematsu T, Takata T
  • Journal Title: J cell Biochem Volume: 112 Pages: 387-393
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 inhibition causes antiangiogenic effects on tumor endothelial and vascular progenitor cells (2011)
  • Author(s): Muraki C, Ohga N, Hida Y, Nishihara H, Kato Y, Tsuchiya K, Matsuda K,Totsuka Y, Shindoh M and Hida K
  • Journal Title: Int J Cancer Volume: 130 Pages: 59-70
• [Journal Article] HuR keeps an angiogenic switch on by stabilizing mRNA of VEGF and COX-2 in tumor endothelium (2011)
  • Author(s): Kurosu T, Ohga N, Hida Y, Maishi N, Akiyama K, Kakuguchi W, Kuroshima T, Kondo M., Akino T., Totsuka Y., Shindoh M,Higashino F and Hida K
  • Journal Title: Br J Cancer Volume: 104(5) Pages: 819-829
• [Journal Article] Phenotype of tumor lymphatic vessels is a prognostic factor in human tongue squamous cell carcinoma (2011)
  • Author(s): Nitta Y, Hida K, Kitamura T, Higashino F, Ohga N, Fukushima K, Shindoh M
  • Journal Title: Oncol Lett Volume: 2(1) Pages: 79-83
• [Journal Article] Nuclear Survivin expression is correlated with malignant behaviors of head and neckcancer together with Aurora-B (2010)
  • Author(s): Qi G, Kudo Y, Ando T, Tsunematsu T, Shimizu N, Siriwardena S, Yoshida M, Keikhaee M, Ogawa I, Takata T
  • Journal Title: Oral Oncol Volume: 46(4) Pages: 263-70
  • Peer Reviewed
• [Journal Article] Isolated tumor endothelial cells maintain specific character during long-term culture (2010)
  • Author(s): Matsuda K, Ohga N, Hida Y, Muraki C, Kurosu T, Tsuchiya K, Akino T., Shih SC, Totsuka Y, Klagsbrun M, Shindoh M and Hida K
  • Journal Title: Biochem Biophys Res Commun Volume: 394 Pages: 947-954
• [Journal Article] Adrenomedullin antagonist suppresses tumor formation in renal cell carcinoma through inhibitory effects on tumor endothelial cells and endothelial progenitor mobilization (2010)
  • Author(s): Tsuchiya K, Hida K, Hida Y, Muraki C, Ohga N, Kondo T, Miseki T, Nakagawa K, Shindoh M, Harabayashi T., Shinohara N, Nonomura K and Kobayashi M
  • Journal Title: Int J Oncol Volume: 36(6) Pages: 1379-1386
• [Journal Article] Oncogenic role of nuclear accumulated Aurora-A. (2009)
  • Author(s): Tatsuka M, Sato S, Kanda A, Miki T, Kamata N, Kitajima S, Kudo Y, Takata T
  • Journal Title: Mol Carcinogen Volume: 48 Pages: 810-820
  • Peer Reviewed
• [Journal Article] Aberrant β-catenin expression and adenomatous polyposis coli gene mutation in ameloblastoma and odontogenic carcinoma (2009)
  • Author(s): Siriwardena BS, Kudo Y, Ogawa I, Tilakaratne WM, Takata T
  • Journal Title: Oral Oncol Volume: 45 Pages: 103-108
  • Peer Reviewed
• [Journal Article] RUNX3 has an oncogenic role in head and neck cancer. (2009)
  • Author(s): Tsunematsu T, Kudo Y, Iizuka S, Ogawa I, Fujita T, Kurihara H, Abiko Y, Takata T
  • Journal Title: PLoS ONE Volume: 4 Pages: e5892
  • Peer Reviewed
• [Journal Article] Inhibitory Effects of Epigallocatechin-3 Gallate, a Polyphenol in Green Tea, on Tumor-Associated Endothelial Cells and Endothelial Progenitor Cells (2009)
  • Author(s): Ohga N, Hida K, Hida Y, Muraki C, Tsuchiya K,Matsuda K, Ohiro Y,Totsuka Y and Shindoh M
  • Journal Title: Cancer Sci Volume: 100(10) Pages: 1963-1970
• [Journal Article] Cytogenetic Abnormalities of Tumor-Associated Endothelial Cells in Human Malignant Tumor (2009)
  • Author(s): Akino T, Hida K,Hida Y, Tsuchiya K, Freedman D, Muraki C, Ohga N, Matsuda K, Harabayashi T, Shinohara N, Nonomura K,KlagsbrunM and Shindoh M
  • Journal Title: Am J Pathol Volume: 175(6) Pages: 2657-2667
• [Presentation] Identification of microRNA-203 as an invasion in oral cancer (2012)
  • Author(s): 大林真理子, 吉田真希, 工藤保誠, 高田 隆
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] FGFR-1 inhibitor PD173074 induces mesenchymal-epithelial tramsition through suppression of AP-1 in Head and Neck Squamous Cel Carcinoma (2012)
  • Author(s): Nguyen PT, Inubushi T, Tsunematsu T, Kudo Y, Kamata N, Ogawa I, Takata T
  • Organizer: 第23回日本臨床口腔病理学会・学術大会
  • Place of Presentation: 東京
  • Year and Date: 2012-08-30
• [Presentation] FGFR-1 inhibitor PD173074 induces mesenchymal-epithelial tramsition through suppression of AP-1 in Head and Neck Squamous Cell Carcinoma (2012)
  • Author(s): Nguyen PT, Inubushi T, Tsunematsu T, Kudo Y, Kamata N, Ogawa I, Takata T
  • Organizer: Cold Spring Harbor Meeting, Models & Mechanisms of Cancer
  • Place of Presentation: New York, USA
  • Year and Date: 2012-08-16
• [Presentation] Identification of microRNA-203 as an inhibitor of invasion in oral cancer (2011)
  • Author(s): Obayashi M, Kudo Y, Yoshida M, Hino Y, Fukunaga S, Tahara H,Takata T
  • Organizer: 59th JADR Annual Meeting
  • Place of Presentation: 広島市
  • Year and Date: 20111008-09
• [Presentation] 口腔癌における浸潤抑制因子としてのmiR-203の同定 (2011)
  • Author(s): 大林真理子,工藤保誠,吉田真希,日野由美子,福永早央里,田原栄俊,高田 隆
  • Organizer: 第30回分子病理学研究会
  • Place of Presentation: 倉敷市
  • Year and Date: 20110722-24
• [Presentation] 頭頸部癌の浸潤に関わる microRNA の探索 (2010)
  • Author(s): 吉田真希,工藤保誠,高田 隆
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 20100922-24
• [Presentation] N-cadherin expression is involved in malignant behavior of head and neck cancer in relation to epithelial-mesenchymal transition (2010)
  • Author(s): Ohbayashi M,Nguyen PT,Kudo Y, Yoshida M,Miyauchi M,Ogawa I,Takata T
  • Organizer: 15th International Congress on Oral Pathology and Medicine
  • Place of Presentation: ソウル, 韓国
  • Year and Date: 20100816-20
• [Presentation] 口腔癌の浸潤における MMP-10 の役割 (2010)
  • Author(s): 工藤保誠,高田 隆
  • Organizer: 第64回日本口腔科学会
  • Place of Presentation: 札幌市
  • Year and Date: 20100624-25
• [Presentation] HSulf-1 は頭頸部癌の浸潤を促進する (2010)
  • Author(s): 吉田真希,工藤保誠,小川郁子,高田 隆
  • Organizer: 第99回日本病理学会
  • Place of Presentation: 東京都
  • Year and Date: 20100427-29
• [Presentation] Identification and characterization of new invasion relating molecules of head and neck squamous cell carcinoma (2010)
  • Author(s): Kudo Y
  • Organizer: The 120th Anniversary of Siriraj Medical School Siriraj Scientific Congress
  • Place of Presentation: バンコク,タイ
  • Year and Date: 2010-08-17
• [Presentation] 口腔癌の浸潤に関与する microRNA の網羅的解析 (2010)
  • Author(s): 吉田真希、工藤保誠、高田 隆
  • Organizer: 第43回広島大学歯学会総会
  • Place of Presentation: 広島市
  • Year and Date: 2010-06-12
• [Presentation] HSulf-1 promotes the invasion of head and neck cancer (2009)
  • Author(s): 吉田真希,工藤保誠,小川郁子,高田 隆
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 20091001-03
• [Presentation] HSulf-1 は頭頚部癌の浸潤を促進する (2009)
  • Author(s): 吉田真希,工藤保誠, ヌーウィン・ティ・フーン・タオ,小川郁子, 高田 隆
  • Organizer: 第20回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 札幌市
  • Year and Date: 20090729-31