Roles of Epstein-Barr virus-associated B-cell lymphoma for peritoneal metastasis of gastric cancer

• Project/Area Number: 15K14389
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Komatsu Masayuki 国立研究開発法人国立がん研究センター, 研究所, リサーチレジデント (10749500)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 未分化型胃がん / 食道扁平上皮がん / エプスタイン・バーウィルス / Bリンパ腫 / 転移 / 腹膜播種 / 中皮 / 細胞株 / 食道がん

Outline of Final Research Achievements

Since metastasis is one of the most common phenotypes and cause of death in various cancers, elucidation of molecular mechanism of metastasis and tumor progression at metastasis foci may lead to development of innovative therapeutic modalities. In this study, we discovered Epstein-Barr virus (EBV)-associated B-cell lymphoma cells (BCL) are highly present at the metastatic foci (e.g. peritoneum and lymph node) of diffuse-type gastric cancer (DGC) and esophageal squamous cell carcinoma patients. By the molecular biological approach, we revealed that the BCL cells contribute tumor survival at peritoneum via activation of the mesothelium in peritoneal metastasis of DGC. Moreover, the BCL cells also promote distal metastasis of DGC cells in vivo. Taken together, these findings indicate that EBV-associated BCL can establish favorable niche for metastasis. Therefore, these BCL cells may be an attractive metastasis control target.

Research Products

• [Journal Article] Preclinical efficacy of Sym004, novel anti-EGFR antibody mixture, in esophageal squamous cell carcinoma cell lines (2017)
  • Author(s): Fukuoka S, Komatsu M, et al.
  • Journal Title: Oncotarget Volume: 8 Issue: 7 Pages: 11020-11029
  • DOI: 10.18632/oncotarget.14209
  • Peer Reviewed
• [Journal Article] SIX1 maintains tumor basal cells via TGF-β pathway and associates with poor prognosis in esophageal cancer (2017)
  • Author(s): Nishimura T, Tamaoki M, Komatsuzaki R, Oue N, Taniguchi H, Komatsu M, Aoyagi K, Minashi K, Chiwaki F, Shinohara H, Tachimori Y, Yasui W, Muto M, Yoshida T, Sakai Y, Sasaki H
  • Journal Title: Cancer Science Volume: 108 Issue: 2 Pages: 216-225
  • DOI: 10.1111/cas.13135
  • Peer Reviewed / Open Access
• [Journal Article] Identification and Characterization of CXCR4-Positive Gastric Cancer Stem Cells (2015)
  • Author(s): Fujita T, Komatsu M, et al
  • Journal Title: PLoS One Volume: 6 Issue: 6 Pages: 1-19
  • DOI: 10.1371/journal.pone.0130808
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Discovery of a Good Responder Subtype of Esophageal Squamous Cell Carcinoma with Cytotoxic T-Lymphocyte Signatures Activated by Chemoradiotherapy. (2015)
  • Author(s): Tanaka Y, Komatsu M, et al
  • Journal Title: PLoS One Volume: 12 Issue: 12 Pages: 1-13
  • DOI: 10.1371/journal.pone.0143804
  • NAID: 120005766970
  • Peer Reviewed / Open Access
• [Journal Article] Implications of epithelial-mesenchymal transition in gastric cancer (2015)
  • Author(s): Tanabe S, Komatsu M, et al
  • Journal Title: Translational Gastrointestinal Cancer Volume: 4 Pages: 258-264
  • Peer Reviewed
• [Presentation] Omics analysis of peritoneally-metastasized diffuse-type gastric cancer cells (2017)
  • Author(s): Masayuki Komatsu
  • Organizer: 89th Annual Meeting of the Japanese Gastric Cancer Association
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2017-03-09
• [Presentation] Omics analysis focused on peritoneally-metastasized cancer cells in diffuse-type gastric cancer (2016)
  • Author(s): Masayuki Komatsu
  • Organizer: The 75th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-06
• [Presentation] Discovery of a chemoradiotherapy-sensitive subtype of esophageal squamous cell carcinomas with high tumor immunity (2015)
  • Author(s): Masayuki Komatsu
  • Organizer: The 74th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
  • Year and Date: 2015-10-08