Identification of tumor vascular miRNA and application to cancer diagnosis and therapy

• Project/Area Number: 15K15726
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: Sato (Kuribayashi) Kazuyo 北海道大学, 歯学研究科, 助教 (70455674)
• Co-Investigator(Kenkyū-buntansha): 間石 奈湖 北海道大学, 遺伝子病制御研究所, 助教 (00632423) ; 秋山 廣輔 北海道大学, 遺伝子病制御研究所, 客員研究員 (10609100) ; 大賀 則孝 北海道大学, 歯学研究科, 助教 (40548202)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: がん / 腫瘍血管 / miRNA

Outline of Final Research Achievements

In this study, we have tried to identify miRNAs which are involved in tumor vessel abnormality and to evaluate their roles in tumor invasion and metastasis, in order to develop novel cancer diagnostics and therapy. Endothelial cells were treated by cancer-derived exosome. Several miRNAs were upregulated and their function were analyzed. Using miRNA database, the target gene of these miRNAs were picked up and the involvement of these target molecule in tumor vessel abnormality were addressed.

Research Products

• [Journal Article] Vasohibin-1 as a novel prognostic factor for head and neck squamous cell carcinoma (2017)
  • Author(s): Torii C., Hida Y., Shindoh M., Akiyama K., Ohga N., Maishi N., Ohiro Y., Ono M., Totsuka Y., Kitagawa Y., Tei K., Sato Y., Hida K.
  • Journal Title: Anticancer Res Volume: 37 Issue: 3 Pages: 1219-1225
  • DOI: 10.21873/anticanres.11437
  • Peer Reviewed / Open Access
• [Journal Article] Aneuploidy of murine immortalized endothelial cell line, MS1. (2017)
  • Author(s): Hida K., Maishi N., Dorcas Akuba-Muhyia Annan, Kondoh M., Hojo T., Umma Habiba, Ohga N., Ishikawa K, Sato M., Torii C., Yanagiya M., Morimoto M., Hida Y., Shindoh M.
  • Journal Title: J Oral Biosci Volume: 59 Issue: 1 Pages: 50-54
  • DOI: 10.1016/j.job.2016.10.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Successful conservative treatment of osteonecrosis of jaw caused by denosumab in patients with multiple bone metastasis. (2017)
  • Author(s): Ohga.N＊, Sato.J , Asaka.T, Moritomoto.M, Yamazaki.Y, Kitagawa,Y
  • Journal Title: Journal of oral science Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Unusual maxillary osteoblastic and osteolytic lesions presenting as an initial manifestation of childhood acute myeloid leukemia: a case report (2017)
  • Author(s): Shimizu.R , Ohga.N＊, Miyakoshi.M , Asaka.T , Sato.J , Kitagawa.Y
  • Journal Title: Quintessence Int Volume: 48(2) Pages: 149-153
• [Journal Article] A case of subcutaneous panniculitis-like T-cell lymphoma of the cheek (2017)
  • Author(s): Sakata.K , Yamazaki.Y, Kuroshima.T, Ohga.N, Satoh.C, Sakakibara.N, Kitagawa.Y
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Tumor endothelial cells express high pentraxin 3 levels (2016)
  • Author(s): Hida K., Maishi N., Kawamoto T., Akiyama K., Ohga N., Hida Y., Yamada K., Hojo T., Kikuchi H., Sato M., Torii C., Shinohara N., Shindoh M
  • Journal Title: Pathol Int Volume: 66 Issue: 12 Pages: 687-694
  • DOI: 10.1111/pin.12474
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of characteristics of mouse immortalized normal endothelial cells, MS1 and primary cultured endothelial cells. (2016)
  • Author(s): Hida K., Maishi N., Torii C., Yanagiya M., Annan Akuba-Muhyia Dorcas., Morimoto M., Alam Mohammad Towfik
  • Journal Title: Hokkaido J. Dent. Sci. Volume: 37 Pages: 40-48
  • NAID: 120005855959
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan. (2016)
  • Author(s): N. Maishi, Y. Ohba, K. Akiyama, N. Ohga, J.I. Hamada, H. Nagao-Kitamoto, M. Alam, K. Yamamoto, T. Kawamoto, N. Inoue, A. Taketomi, M. Shindoh, Y. Hida and K. Hida.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 28039-28039
  • DOI: 10.1038/srep28039
  • NAID: 120005819304
  • Peer Reviewed / Open Access
• [Journal Article] 下顎骨骨髄から発生したと考えられた巨大な悪性リンパ腫の１例 (2016)
  • Author(s): 山田珠希，栗林和代，大廣洋一，篠原早紀，松田光平，鈴木豊典，北村哲也，進藤正信，鄭 漢忠
  • Journal Title: 北海道歯学雑誌 Volume: 36(2) Pages: 134-141
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evaluation of the level of progression of extracapsular spread for cervical lymph node metastasis in oral squamous cell carcinoma. (2016)
  • Author(s): Yamada S, Yanamoto S, Otani S, Hasegawa T, Miyakoshi M, Minamikawa T, Ohga N, Kamata T, Komori T, Kitagawa Y, Kurita H, Umeda M.
  • Journal Title: Int J Oral Maxillofac Surg Volume: 45(2) Issue: 2 Pages: 141-6
  • DOI: 10.1016/j.ijom.2015.09.005
  • Peer Reviewed / Open Access
• [Journal Article] CXCL 12-CXCR7 axis is important for tumor endothelial cell angiogenic property (2015)
  • Author(s): Yamada K., Maishi N., Akiyama K., Alam Mohammad Towfik, Ohga N., Kawamoto T., Shindoh M. Takahashi N., Kamiyama T., Hida Y., Taketomi A. and Hida K.
  • Journal Title: Int J Cancer Volume: 137(12) Issue: 12 Pages: 2825-2836
  • DOI: 10.1002/ijc.29655
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of multidrug transporter in tumor endothelial cells enhances antiangiogenic effects of low-dose metronomic paclitaxel (2015)
  • Author(s): 1.Akiyama K., Maishi N., Ohga N., Hida Y., Ohba Y., Alam Mohammad Towfik, Kawamoto T., Ohmura H., Yamada K., Torii C., Shindoh M. and *Hida K.
  • Journal Title: Am J Pathol Volume: 185(2) Issue: 2 Pages: 572-580
  • DOI: 10.1016/j.ajpath.2014.10.017
  • Peer Reviewed / Open Access
• [Journal Article] Differences in sequential posttreatment salivary IL-6 levels between patients with and patients without locoregional recurrences of oral squamous cell carcinoma: Part III of a cohort study. (2015)
  • Author(s): Sato J, Ohuchi M, Wada M, Ohga N, Asaka T, Yoshikawa K, Miyakoshi M, Hata H, Satoh A, Kitagawa Y.
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol Volume: 120 Issue: 6 Pages: 751-60
  • DOI: 10.1016/j.oooo.2015.08.016
  • Peer Reviewed / Open Access
• [Journal Article] Marked bone production from the mandibular head to the reconstructed fibula after chemoradiotherapy for the recurrent tumor. (2015)
  • Author(s): Satoh A., Ohga N., Asaka T., Kitagawa Y.
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 27(6) Issue: 6 Pages: 829-833
  • DOI: 10.1016/j.ajoms.2015.04.005
  • Peer Reviewed / Open Access
• [Journal Article] Dose escalation effectiveness and tolerability of paroxetine in patients with burning mouth syndrome and depressive conditions. (2015)
  • Author(s): Ohga N., Yamazaki Y., Sato J., Hata H., Murata T., Sakata K., Inoue T., Kitagawa Y.
  • Journal Title: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology Volume: 27(3) Issue: 3 Pages: 402-406
  • DOI: 10.1016/j.ajoms.2015.02.001
  • Peer Reviewed / Open Access
• [Journal Article] Healing of osteonecrosis of the jaw (ONJ) after discontinuation of denosumab in a patient with bone metastases of colorectal cancer: a case report and hypothesis. (2015)
  • Author(s): Ohga N., Yamazaki Y., Tsuboi K., Kitagawa Y.
  • Journal Title: Quintessence International Volume: 46(7) Pages: 621-626
  • Peer Reviewed
• [Presentation] 腫瘍血管内皮細胞によるBiglycanの分泌を介したがんの転移促進 (2017)
  • Author(s): 間石奈湖
  • Organizer: 第２回口腔医科学フロンティア研究会
  • Place of Presentation: ZAOセンタープラザ 山形
• [Presentation] Tumor Endothelial Cells Promote Metastasis via Biglycan (2016)
  • Author(s): Maishi N.
  • Organizer: Keystone Symposia on Molecular and Cellular Biology
  • Place of Presentation: Breckenridge, Colorado, USA
  • Year and Date: 2016-03-30
  • Int'l Joint Research
• [Presentation] 腫瘍分泌小胞miRNAによる血管内皮の薬剤耐性誘 (2016)
  • Author(s): 鳥居ちさほ，間石奈湖，樋田京子
  • Organizer: 第2回血管生物若手研究会
  • Place of Presentation: 東北大学（宮城県仙台市）
  • Year and Date: 2016-03-04
• [Presentation] Correlation between CXCR7 expression of blood vessels and clinicopathological features in oral squamous cell carcinoma (2016)
  • Author(s): 柳谷美沙，間石奈湖，鳥居ちさほ，樋田泰浩，大賀則孝，鄭 漢忠，進藤正信，北川善政，樋田京子
  • Organizer: 第24回日本血管生物医学会学術集会
  • Place of Presentation: 長崎ブリックホール 長崎
• [Presentation] Tumor endothelial cells acquire drug resistance by exosomal-miR derived from high metastatic tumor (2016)
  • Author(s): Hida K., Torii C., Maishi N., Morimoto M., Akiyama K., Kawamoto T., Minami T., Yoshioka Y., Mohammad Towfik Alam, Shindoh M., Hida Y., Ochiya T
  • Organizer: The 19th International Vascular Biology Meeting, 2016. 11.2, Boston, Massachusetts
  • Place of Presentation: Sheraton Boston Hotel, Boston, Massachusetts, USA
  • Int'l Joint Research
• [Presentation] Tumor endothelial cells in high metastatic tumors promote metastasis via biglycan (2016)
  • Author(s): Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Nagao-Kitamoto H., Mohammad Towfik Alam, Shindoh M., Hida Y. Hida K.
  • Organizer: The 19th International Vascular Biology Meeting
  • Place of Presentation: Sheraton Boston Hotel,Boston, Massachusetts, USA
  • Int'l Joint Research
• [Presentation] 腫瘍血管内皮細胞によるがん転移促進 (2016)
  • Author(s): 間石奈湖，樋田京子
  • Organizer: 第75回日本癌学会学術総会特別シンポジウム２「癌研究における女性研究者」
  • Place of Presentation: パシフィコ横浜 横浜
  • Invited
• [Presentation] 活性酸素が腫瘍血管内皮細胞に及ぼす影響 (2016)
  • Author(s): 間石 奈湖、樋田 京子
  • Organizer: 第 69 回日本酸化ストレス学会学術集会シンポジウム「酸化ストレスと発がん～最新の知見～」
  • Place of Presentation: 仙台国際センター会議棟 仙台
  • Invited
• [Presentation] 腫瘍血管内皮細胞によるbiglycanの分泌を介したがんの転移促進 (2016)
  • Author(s): 間石奈湖，秋山廣輔，大賀則孝，浜田淳一，樋田京子
  • Organizer: 第25回日本がん転移学会学術集会・総会
  • Place of Presentation: 米子コンベンションセンター 米子
• [Presentation] 腫瘍血管内皮細胞によるがん転移促進 (2016)
  • Author(s): 間石奈湖
  • Organizer: 第12回北海道癌免疫制御研究会
  • Place of Presentation: メルキュールホテル札幌 札幌
• [Presentation] Evaluation of Bone Height in Osseous Mandibular Reconstruction Using Free Fibular Grafts (2015)
  • Author(s): Sato K., Ishikawa K., Ashikaga Y., Ohiro Y., Ono M., Hayashi T., Tei K.
  • Organizer: Face Restoration in Maxillofacial & Plastic Surgery
  • Place of Presentation: St. Anna Hospital & University (Ferrara-Cona, Italy)
  • Year and Date: 2015-11-13
• [Presentation] ROS によるbiglycan 発現誘導を介した腫瘍血管内皮細胞の血管新生能亢進 (2015)
  • Author(s): 北條敬之，間石奈湖，Mohammad T Alam，秋山廣輔，大賀則孝，進藤正信，樋田泰浩，藤澤俊明，樋田京子
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-10
• [Presentation] 高転移性腫瘍miRNA はIL-6 ならびにALDH の発現亢進を介して血管内皮に薬剤耐性を誘導する (2015)
  • Author(s): 鳥居ちさほ，秋山廣輔，川本泰輔，間石奈湖，鄭漢忠，戸塚靖則，進藤正信，樋田泰浩，南敬，小坂展慶，落谷孝広，樋田京子
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-10
• [Presentation] 腫瘍血管内皮細胞はbiglycan の分泌を介してがんの転移を促進する (2015)
  • Author(s): 間石奈湖，大場雄介，秋山廣輔，大賀則孝，浜田淳一，北本(永尾）宗子，Mohammad Alam T.，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Tumor endothelial cells promote metastasis via biglycan secretion (2015)
  • Author(s): Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Mohammad Towfik Alam, Shindoh M., Hida Y., Hida K
  • Organizer: The European Cancer Congress 2015
  • Place of Presentation: Messe Wien Exhibition & Congress Centre (Vienna, Austria)
  • Year and Date: 2015-09-27
  • Int'l Joint Research
• [Presentation] Tumor Endothelial cell-secreted protein activates a DNA damage response (2015)
  • Author(s): Annan Dorcas A., 間石奈湖，北條敬之，鳥居ちさほ，Mohammad T Alam.，Habiba Umma，樋田泰浩，樋田京子
  • Organizer: 第112回北海道癌談話会例会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-09-12
• [Presentation] 高転移性腫瘍miRによらう血管内皮におけるIL-6を介した薬剤耐性誘導 (2015)
  • Author(s): 鳥居ちさほ，秋山廣輔，川本泰輔，間石奈湖，Alam Mohammad Towfik，鄭 漢忠，戸塚靖則，進藤正信，樋田泰浩，南 敬，小坂展慶，落谷孝広，樋田京子
  • Organizer: 第112回北海道癌談話会例会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-09-12
• [Presentation] 腫瘍血管内皮細胞はbiglycanの分泌を介してがんの転移を促進する (2015)
  • Author(s): 間石奈湖，大場雄介，秋山廣輔，大賀則孝，浜田淳一，北本宗子，Alam Mohammad Towfik，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-07-31
• [Presentation] 高転移性腫瘍miRNAはIL-6ならびにALDHの発現亢進を介して血管内皮に薬剤耐性を誘導する (2015)
  • Author(s): 鳥居ちさほ，秋山廣輔，川本泰輔，間石奈湖，鄭 漢忠，戸塚靖則，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-07-31
• [Presentation] Suprabasin as a novel tumor endothelial cell marker (2015)
  • Author(s): Alam Mohammad Towfik，Nagao-Kitamoto H., Ohga N., Akiyama K., Maishi N., Kawamoto T, Shinohara N., Taketomi A., Shindoh M, Hida Y, Hida K
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-07-31
• [Presentation] 活性酸素種によるBiglycan発現誘導を介した腫瘍血管内皮細胞の血管新生能亢進 (2015)
  • Author(s): 北條敬之，間石奈湖，秋山廣輔，大賀則孝，進藤正信，樋田泰浩，藤澤俊明，樋田京子
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-07-31
• [Presentation] 腫瘍血管内皮細胞はbiglycanの分泌を介してがんの転移を促進する (2015)
  • Author(s): 間石奈湖
  • Organizer: 第24回日本がん転移学会学術集会・総会
  • Place of Presentation: シティプラザ大阪（大阪府大阪市）
  • Year and Date: 2015-07-23
• [Presentation] 腫瘍微小環境において，腫瘍由来のmiRX により血管内皮はIL-6 をオートクラインで利用し，薬剤耐性や幹細胞性を獲得している (2015)
  • Author(s): 鳥居ちさほ，秋山廣輔，川本泰輔，間石奈湖，鄭 漢忠，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第69回日本口腔科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-05-14
• [Presentation] 局所進行口腔扁平上皮癌における術前DOC・CDDP同時併用化学放射線療法の治療効果 (2015)
  • Author(s): 佐藤和代，大廣洋一，足利雄一，小野貢伸，北村哲也，進藤正信，鄭 漢忠
  • Organizer: 第69回日本口腔科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-05-14
• [Presentation] Tumor endothelial cells instigate metastasis of indolent tumors (2015)
  • Author(s): Maishi N., Hida K.
  • Organizer: Spring Special Symposium of the Japanese Vascular Biology and Medicine Organization
  • Place of Presentation: 大阪大学微生物病研究所（大阪府吹田市）
  • Year and Date: 2015-05-13
  • Invited
• [Book] 別冊BIO Clinica 慢性炎症と疾患～慢性炎症とがん (2016)
  • Author(s): 樋田京子，大賀則孝，間石奈湖，秋山廣輔，樋田泰浩
  • Total Pages: 172
  • Publisher: 北隆館