Analysis of the metastatic activity of headn and neck cancer from the asepect of lymphangiogenesis

• Project/Area Number: 25462915
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Tohto College of Health Sciences
• Principal Investigator: Katsube Ken-ichi 東都医療大学, ヒューマンケア学部, 教授 (20233760)
• Co-Investigator(Kenkyū-buntansha): 栢森 高 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (10569841)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Notch / 脈管新生 / 癌転移 / 腫瘍 / 血管 / リンパ管 / 血管新生 / VEGF / 癌細胞 / 癌 / 骨髄幹細胞 / notch / Notch3 / CAF / 癌幹細胞 / 扁平上皮癌

Outline of Final Research Achievements

Coculture of the oral Squamous cell carcinoma (SCC) and fibroblasts showed the significant upregulation of Notch3 among Notch receptor family. Separation analysis revealed that the fibroblasts are responsible for Notch3 upregulation and carcinoma cells express JAG1. Triple coculture of oral SCC, fibroblasts and HUVEC showed an accelerated vasculogenesis. Oral SCC cell lines are classified into Notch3-inducing type and Notch3-non-inducing type, in which the Notch3-inducing cell lines have highly active growth in vivo. Analysis of the clinical cases of oral SCC revealed that Notch3-inducing type has higher malignant activity. Oral SCC may induce not only CAF to produce an favorable environment, but also vasculogenesis to promote metastasis.

Research Products

• [Journal Article] The Bone Regeneration Model and Primary Osteoblastic Cell Culture Used in the Analysis of Ccn3 Transgenic and Knockout Mice (2017)
  • Author(s): Sakamoto K, Matsushita Y, Minamizato T, Katsuki Y, Katsube K, Yamaguchi A.
  • Journal Title: Methods Mol Biol. Volume: ;1489 Pages: 309-324
  • DOI: 10.1007/978-1-4939-6430-7_27
  • ISBN: 9781493964284, 9781493964307
  • Peer Reviewed
• [Journal Article] KRT17 is induced in oral cancer and facilitate tumor gowth. (2016)
  • Author(s): Khanom R, Nguyen CTK, Kayamori K, Zhao X, Morita K, Yamaguchi A, Sakamoto K
  • Journal Title: PlosOne Volume: 11 Issue: 8 Pages: e0161163-e0161163
  • DOI: 10.1371/journal.pone.0161163
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Recent advances in renal cell carcinoma from a pathological point of view. (2016)
  • Author(s): Mikami S, Oya M, Mizuno R, Kosaka T, Ishida M, Kuroda N, Nagashima Y, Katsube K, Okada Y.
  • Journal Title: Pathol Int. Volume: 66 Issue: 9 Pages: 481-90
  • DOI: 10.1111/pin.12433
  • Peer Reviewed / Open Access
• [Journal Article] NOTCH3 Is Induced in Cancer-Associated Fibroblasts and Promotes Angiogenesis in Oral Squamous Cell Carcinoma (2016)
  • Author(s): Kayamori K, Katsube K, Sakamoto K, Ohyama Y, Hirai H, Yukimori A, Ohata Y, Akashi T, Saitoh M, Harada K, Harada H, Yamaguchi A
  • Journal Title: PLoS ONE Volume: 11 Issue: 4 Pages: 223-231
  • DOI: 10.1371/journal.pone.0154112
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A facile one-step strategy for the generation of conditional knockout mice to explore the role of Notch1 in oroesophageal tumorigenesis. (2016)
  • Author(s): Mandasari M, Sawangarun W, Katsube K, Kayamori K, Yamaguchi A, Sakamoto K
  • Journal Title: Biochem Biophys Res Commun Volume: 469(3) Issue: 3 Pages: 761-767
  • DOI: 10.1016/j.bbrc.2015.12.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A facile one-step strategy for the generation of conditional knockout mice to explore the role of Notch1 in oroesophageal tumorigenesis. (2016)
  • Author(s): Mandasari M, Sawangarun W, Katsube K, Kayamori K, Yamaguchi A, Sakamoto K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 469 Pages: 761-767
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ビッグデータと看護・医療の将来 (2014)
  • Author(s): 勝部憲一
  • Journal Title: 東都医療大学紀要 Volume: 5巻 Pages: 1-5
  • Peer Reviewed / Open Access
• [Journal Article] Invasion and metastasis of renal cell carcinoma (2013)
  • Author(s): Mikami S, Oya M, Mizuno R, Kosaka T, Katsube KI, Okada Y
  • Journal Title: Med Mol Morphol Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Integrated genotypic analysis of hedgehog-related genes identifies subgroups of keratocystic odontogenic tumor with distinct clinicopathological features. (2013)
  • Author(s): Shimada Y, Katsube K, Kabasawa Y, Morita K, Omura K, Yamaguchi A, Sakamoto K
  • Journal Title: Plos One Volume: 8 Issue: 8 Pages: e70995-e70995
  • DOI: 10.1371/journal.pone.0070995
  • Peer Reviewed
• [Journal Article] CCN3 protein participates in bone regeneration as an inhibitory factor. (2013)
  • Author(s): Matsushita Y, Sakamoto K, Tamamura Y, Shibata Y, Minamizato T, Kihara T, Ito M, Katsube K, Hiraoka S, Koseki H, Harada K, Yamaguchi A.
  • Journal Title: The Journal of Biological Chemistry Volume: 288 Issue: 27 Pages: 19973-19985
  • DOI: 10.1074/jbc.m113.454652
  • Peer Reviewed