Phagocytosis of apoptotic cells by oral squamous cell carcinoma cells: a possible driving force for cancer progression

• Project/Area Number: 15K11006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Niigata University
• Principal Investigator: Yamazaki Manabu 新潟大学, 医歯学系, 助教 (10547516)
• Co-Investigator(Kenkyū-buntansha): 阿部 達也 新潟大学, 医歯学総合研究科, 特任助教 (70634856) ; 丸山 智 新潟大学, 医歯学総合病院, 講師 (30397161) ; 程 クン 新潟大学, 医歯学系, 准教授 (40207460) ; 朔 敬 大阪歯科大学, 歯学部, 客員教授 (40145264)
• Project Period (FY): 2015-04-01 – 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 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 口腔がん / 病理学 / アポトーシス / 貪食 / 口腔癌

Outline of Final Research Achievements

Apoptotic cancer cells are cleaned by macrophages and also by the neighboring cancer cells. Based on a hypothesis that apoptotic cell clearance by living carcinoma cells could contribute to cancer cell activities and tumor progression, we investigated a biological significance of this phenomenon using cultured cell lines derived from oral squamous cell carcinoma. When co-cultured with UV-induced apoptotic cells, the most of living cells engulfed apoptotic cells, and this engulfment was inhibited by Rac1 inhibitor. Electron microscopy demonstrated the engulfed cells localized within the phagosomes, with which the lysosomes seem to fuse. Furthermore, co-culture with apoptotic cells enhanced migration and invasion. These results suggested that self-clearance may upregulate cancer cell activities. Control of self-clearance in cancer would open up a new direction for therapeutic intervention.

Research Products

• [Journal Article] Proteomic and histopathological characterization of the interface between oral squamous cell carcinoma invasion fronts and non-cancerous epithelia (2017)
  • Author(s): Abe T, Maruyama S, Yamazaki M, Xu B, Babkair H, Sumita Y, Cheng J, Yamamoto T, Saku T
  • Journal Title: Experimental and Molecular Pathology Volume: 102 Issue: 2 Pages: 327-336
  • DOI: 10.1016/j.yexmp.2017.02.018
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Concomitant expression of ezrin and HER2 predicts distant metastasis and poor prognosis of patients with salivary gland carcinomas. (2017)
  • Author(s): Hashimoto K, Hayashi R, Mukaigawa T, Yamazaki M, Fujii S.
  • Journal Title: Human Pathology Volume: 印刷中 Pages: 110-119
  • DOI: 10.1016/j.humpath.2017.02.017
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma (2016)
  • Author(s): Babkair H, Yamazaki M, Uddin MS, Maruyama S, Abe T, Essa A, Sumita Y, Ahsan MS, Swelam W, Cheng J, Saku T
  • Journal Title: Human Pathology Volume: 57 Pages: 51-60
  • DOI: 10.1016/j.humpath.2016.07.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tumor-associated macrophages are recruited and differentiated in the neoplastic stroma of oral squamous cell carcinoma. (2016)
  • Author(s): Essa AAM, Yamazaki M, Maruyama S, Abe T, Babkair H, Raghib AM, Megahed EMED, Cheng J, Saku T.
  • Journal Title: Pathologｙ Volume: 48（3） Issue: 3 Pages: 219-227
  • DOI: 10.1016/j.pathol.2016.02.006
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 口腔癌治療後に生じたbizarre stromal reactionの2例 (2017)
  • Author(s): 山崎 学, 隅田賢正, 丸山 智, 阿部達也, 程 クン, 朔 敬.
  • Organizer: 第106回日本病理学会総会
• [Presentation] Apoptotic cell clearance upregulates cancer cell activities in oral squamous cell carcinoma. (2016)
  • Author(s): Yamazaki M, Maruyama S, Abe T, Babkair H, Sumita Y, Cheng J
  • Organizer: 第27回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 広島大学（広島県広島市）
  • Year and Date: 2016-08-10
• [Presentation] がん細胞による死細胞処理：その生物学的意義. (2016)
  • Author(s): 山崎 学, 丸山 智, 阿部達也, 近藤英作, 程 クン
  • Organizer: 第13回日本病理学会カンファレンス
  • Place of Presentation: 六甲山ホテル（兵庫県神戸市）
  • Year and Date: 2016-07-29
• [Presentation] Inflammatory but not develcomantal histopathogenesis of intraoral lymphoepithelial cyst. (2016)
  • Author(s): 山崎 学, 丸山 智, 阿部達也, バブカイール ハムザ, 隅田賢正, 程 クン, 朔 敬
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-05-12
• [Presentation] 口腔扁平上皮癌細胞による死細胞貪食の分子機構とその意義 (2015)
  • Author(s): 山崎 学
  • Organizer: 第57回歯科基礎医学会学術大会・総会
  • Place of Presentation: 新潟市 朱鷺メッセ
  • Year and Date: 2015-09-11
• [Presentation] GAS6/MERTK axis in oral squamous cell carcinoma: a possible mechanism for apoptotic cancer cell clearance by cancer cells and macrophages. (2015)
  • Author(s): 山崎 学，丸山 智，阿部 達也，程 クン，朔 敬
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 札幌市 北海道大学学術交流会館
  • Year and Date: 2015-07-29
• [Presentation] MFG-E8 expression for progression and self-clearance of apoptotic cells in oral squamous cell carcinoma. (2015)
  • Author(s): Yamazaki M
  • Organizer: The 4th International Conference and Exhibition on Pathology
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2015-07-13
  • Int'l Joint Research