Epithelial and mesenchymal cross-talk on mechanism of bone invasion of ameloblastoma

• Project/Area Number: 26463019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kagoshima University
• Principal Investigator: NAKAMURA Norifumi 鹿児島大学, 医歯学域歯学系, 教授 (60217875)
• Co-Investigator(Kenkyū-buntansha): 岸田 昭世 鹿児島大学, 医歯学域医学系, 教授 (50274064) ; 岐部 俊郎 鹿児島大学, 医歯学域附属病院, 助教 (50635480) ; 岸田 想子 鹿児島大学, 医歯学域医学系, 助教 (40274089)
• Co-Investigator(Renkei-kenkyūsha): KIBE Toshiro 鹿児島大学, 医歯学域歯学系, 助教 (50635480)
• Research Collaborator: KISHIDA Michiko 鹿児島大学, 医歯学域医学系, 助教 (40274089)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 歯原性腫瘍 / 上皮-間葉相互作用 / エナメル上皮腫 / 骨浸潤 / エナメル上皮腫上皮腫 / インターロイキン / 腫瘍間質 / 線維芽細胞 / 相互作用

Outline of Final Research Achievements

Analyses of the interaction, cross-talk, between ameloblstoma cell (AM-3) and fibroblast cell (HFF-2) revealed that AM-3 secreted IL-α and facilitated of IL-6 and IL-8 secretion of HFF-2 fibroblasts, and stimulation by the cocultured supernatant of both cells accelerated the migration activity of AM-3. These findings suggest that the ameloblastoma cells and stromal fibroblasts behave interactively via cytokines to create a microenvironment that leads to the extension of ameloblastomas.
Three dimensional observation using double layered collagen gel hemisphere culture revealed that AM-3 cells formed tuft-like invasive processes and collectively invaded into outer layer. These findings were more apparent under the presence of HEF-2 fibroblasts when compared to the single culture of AM-3. HFF-2 fibroblasts localized to the tips of the invasive tumor processes, suggesting that tumor-associated cells assist tumor cell invasion.

Research Products

• [Journal Article] Fibroblasts promote the collective invasion of ameloblastoma tumor cells in a 3D coculture model (2017)
  • Author(s): Fuchigami T, Koyama H, Kishida M, Nishizawa Y, Iijima M, Kibe T, Ueda M, Kiyono T, Maniwa Y, Nakamura N, Kishida S
  • Journal Title: FEBS Open Bio Volume: 7 Issue: 12 Pages: 2000-2007
  • DOI: 10.1002/2211-5463.12313
  • NAID: 120006380405
  • Peer Reviewed / Open Access
• [Journal Article] Afatinib radiosensitizers head and neck squamous cell carcinoma cells by affecting cancer stem cells. (2017)
  • Author(s): Macha M, Rachagani S, Qazi A, Jahan R, Gupta S, Patel A, Seshacharyulu P, Lin C, Li S, Wang S, Verma V, Kishida S, Kishida M, Nakamura N, Kibe T, Lydiatt W, Smith L,Ganti A, Jones D, Batra S, Jain M
  • Journal Title: Oncotarget Journal Volume: 8 Issue: 13 Pages: 20961-20973
  • DOI: 10.18632/oncotarget.15468
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Vascular Endothelial Growth Factor-C Induces Osteogenic Differentiation of Human Mesenchymal Stem Cells through the ERK and RUNX2 Pathway (2017)
  • Author(s): Murakami J, Ishii M, Suehiro F, Ishihata k, Nakamura N, Nishimura M
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 484 Issue: 3 Pages: 710-718
  • DOI: 10.1016/j.bbrc.2017.02.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Snail expression in human colon cancer DLD-1 cells confers invasive properties without N-cadherin expression. (2016)
  • Author(s): Shoko Tanaka, Wakako Kobayashi, Misako Haraguchi, Kiyohide Ishihata, Norifumi Nakamura, Masayuki Ozawa
  • Journal Title: Biochemical and Biophysical Reports Volume: 8 Pages: 120-126
  • DOI: 10.1016/j.bbrep.2016.08.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] エナメル上皮腫に対する顎骨切除・腸骨移植による下顎骨再建後に下顎骨後方移動術を行った1例 (2016)
  • Author(s): 野添悦郎、石畑清秀、大河内孝子、下松孝太、松本幸三、窪田憲司、国広貴玄、宮脇正一、中村典史
  • Journal Title: 日本顎変形症学会雑誌 Volume: 26 Pages: 220-227
  • Peer Reviewed
• [Journal Article] Novel roles for PCP4/PEP19 in the migration,invasion and, adhesion in MCF-7 human breast cancer cells. (2016)
  • Author(s): Takuya Yoshimura, Taiji Hamada, Hiroshi Hijioka, Masakazu Souda, Kazuhito Hatanaka, Takako Yoshioka, Sohsuke Yamada, Masato Tsutsui, Yoshihisa Umekita, Norifumi Nakamura, Akihide Tanimoto
  • Journal Title: Oncotarget Journal Volume: 00
  • Peer Reviewed
• [Journal Article] Primary intraosseous squamous cell carcinoma in association with recurrent ameloblastoma of the mandible: A case report. (2015)
  • Author(s): Hiroshi Hijioka, Hajime Suzuki, Kazuhide Nishihara, Akihiko Miyawaki, Takayuki Ishida, Ichiro Semba, Norifumi Nakamura
  • Journal Title: J Oral Maxillofacial Surgery, Oral Pathology, Oral Medicine Volume: 27 Issue: 5 Pages: 693-697
  • DOI: 10.1016/j.ajoms.2015.02.004
  • Peer Reviewed
• [Journal Article] Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma Biochemical and Biophysical Research Communications (2014)
  • Author(s): Takao Fuchigami, Toshiro Kibe, Hirofumi Koyama, Shosei Kishida, Mikio Iijima, Yoshiaki Nishizawa, Hiroshi Hijioka, Tomomi Fujii, Masahiro Ueda, Norifumi Nakamura, Tohru Kiyono, Michiko Kishida
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 451 Issue: 4 Pages: 491-496
  • DOI: 10.1016/j.bbrc.2014.07.137
  • Peer Reviewed
• [Presentation] The presence of stromal fibroblasts affect the collective cellular migration of tumor cells in ameloblastoma (2017)
  • Author(s): Fuchigami Takao, Shosei Kishida, Toshiro Kibe, Norifumi Nakamura
  • Organizer: 23rd International Conference on Oral and Maxillofacial Surgery
  • Place of Presentation: HongKong China
  • Year and Date: 2017-03-31
  • Int'l Joint Research
• [Presentation] The presence of stromal fibroblasts affect on the collective cellular migration of tumor cells in ameloblastoma (2017)
  • Author(s): Fuchigami T, Kishida S, Kibe T, Nakamura N
  • Organizer: 23th International Conference on Oral and Maxillofacial Surgery
  • Int'l Joint Research
• [Presentation] エナメル上皮腫におけるIL-1α依存性のMMP-9分泌は腫瘍細胞の浸潤に重要である (2017)
  • Author(s): 渕上貴央，岸田昭世，岐部俊郎，石畑清秀，中村典史
  • Organizer: 第71回日本口腔科学会学術集会
• [Presentation] Ameloblastoma -Diagnosis and treatment based on the growth characteristics- (2016)
  • Author(s): Norifumi Nakamura
  • Organizer: Invited lecture at Dental Faculty, Airlangga University
  • Place of Presentation: Surabaya, Indonesia
  • Year and Date: 2016-07-20
  • Invited
• [Presentation] エナメル上皮腫の病態解明に有用な蛍光蛋白質安定発現細胞株を用いた新規三次元共培養実験系の構築 (2016)
  • Author(s): 渕上貴央，岸田昭世，岐部俊郎，中村典史
  • Organizer: 第70回日本口腔科学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡県・福岡市）
  • Year and Date: 2016-04-15
• [Presentation] エナメル上皮種の浸潤発育メカニズムにおける上皮-間葉クロストーク (2016)
  • Author(s): 渕上貴央, 岐部俊郎, 小山浩史, 岸田想子, 中村典史, 岸田昭世
  • Organizer: 第80回日本口腔科学会総会・学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-04-15
• [Presentation] エナメル上皮腫の開窓治療 (2015)
  • Author(s): 中村典史
  • Organizer: 第69回日本口腔外科学会総会・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] 歯原性良性腫瘍であるエナメル上皮腫におけるIL-1αを介した間質線維芽細胞との相互作用 (2014)
  • Author(s): 渕上貴央, 岐部俊郎, 小山浩史, 岸田想子, 中村典史, 岸田昭世
  • Organizer: 第37回 日本分子生物学会年会
  • Place of Presentation: 横浜市、パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Ameloblastoma-Diagnosis and treatment based on the growth characteristics. (2014)
  • Author(s): Norifumi Nakamura
  • Organizer: Invited Seminar at University of Indonesia
  • Place of Presentation: Jakarta, Indonesia
  • Year and Date: 2014-11-11
  • Invited
• [Presentation] エナメル上皮腫の微小環境の解明 -IL-1αを介した間質線維芽細胞との相互作用- (2014)
  • Author(s): 渕上貴央, 岐部俊郎, 小山浩史, 岸田想子, 中村典史, 岸田昭世
  • Organizer: 第59回 公益社団法人 日本口腔外科学会総会・学術大会
  • Place of Presentation: 千葉市、幕張メッセ
  • Year and Date: 2014-10-17 – 2014-10-19