Analysis for intraperitoneal cancer microenvironment to elucidate the biological mechanism of peritoneal metastasis of gastrointestinal cancer

• Project/Area Number: 15K15193
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Okayama University
• Principal Investigator: Shunsuke Kagawa 岡山大学, 大学病院, 准教授 (00362971)
• Co-Investigator(Kenkyū-buntansha): 吉田 龍一 岡山大学, 大学病院, 助教 (80534768)
• Co-Investigator(Renkei-kenkyūsha): KURODA Shinji 岡山大学, 大学病院, 助教 (60633758) ; NAGASAKA Takeshi 岡山大学, 大学病院, 講師 (30452569) ; TAZAWA Hiroshi 岡山大学, 大学病院, 准教授 (90415513)
• Research Collaborator: FUJIWARA Toshiyoshi 岡山大学, 医歯薬学総合研究科, 教授 (00304303)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 消化器癌 / 腹膜播種 / 癌微小環境 / マクロファージ / 抗癌剤抵抗性 / 腫瘍微小環境 / 膵癌 / 腹腔内遊離癌細胞 / 腫瘍関連マクロファージ

Outline of Final Research Achievements

Gastrointestinal cancer develops peritoneal dissemination, which is known to be refractory to current therapy. To overcome it, cancer microenvironment is need to be analyzed. For analysis of cells constituting the intraperitoneal microenvironment, we obtained peritoneal lavage fluid from patients with stomach cancer and pancreatic cancer and employed cancer-specific GFP expression virus TelomeScan to label cancer cell and immunostaining, which revealed the prevalence of tumor-associated macrophages (TAM) in the peritoneal cavity. Under the co-culture of stomach cancer or pancreatic cancer cells with TAM, the epithelial to mesenchymal transition of cancer cells, the enhancement of malignant phenotypes such as infiltration, migration, and acquired resistance to the chemotherapeutic agents were observed. These results suggested that intraperitoneal microenvironment, especially TAM, may contribute to the refractoriness of gastrointestinal tumor peritoneal dissemination.

Research Products

• [Journal Article] Outcome of Radiation Monotherapy for High-risk Patients with Stage I Esophageal Cancer (2017)
  • Author(s): Shirakawa Y, Noma K, Maeda N, Tanabe S, Kuroda S, Kagawa S, Katsui K, Katayama N, Kanazawa S, Fujiwara T.
  • Journal Title: Acta Medica Okayama Volume: 71 Issue: 2 Pages: 127-133
  • DOI: 10.18926/AMO/54981
  • NAID: 120006026999
  • URL: https://ousar.lib.okayama-u.ac.jp/54981
  • Peer Reviewed / Open Access
• [Journal Article] Tumor-specific delivery of biologics by a novel T-cell line HOZOT. (2016)
  • Author(s): Onishi T, Tazawa H, Hashimoto Y, Takeuchi M, Otani T, Nakamura S, Sakurai F, Mizuguchi H, Kishimoto H, Umeda Y, Shirakawa Y, Urata Y, Kagawa S, Fujiwara T.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 38060-38060
  • DOI: 10.1038/srep38060
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Training system for laparoscopy-assisted distal gastrectomy. (2016)
  • Author(s): Kuroda S, Kikuchi S, Hori N, Sakamoto S, Kagawa T, Watanabe M, Kubota T, Kuwada K, Ishida M, Kishimoto H, Uno F, Nishizaki M, Kagawa S, Fujiwara T
  • Journal Title: Surgery today Volume: 印刷中 Issue: 7 Pages: 802-809
  • DOI: 10.1007/s00595-016-1439-9
  • Peer Reviewed
• [Journal Article] Nonexposure laparoscopic and endoscopic cooperative surgery (closed laparoscopic and endoscopic cooperative surgery) for gastric submucosal tumor (2016)
  • Author(s): Kikuchi S, Nishizaki M, Kuroda S, Tanabe S, Noma K, Kagawa S, Shirakawa Y, Kato H, Okada H, Fujiwara T
  • Journal Title: Gastric Cancer Volume: 20 Issue: 3 Pages: 553-557
  • DOI: 10.1007/s10120-016-0641-1
  • NAID: 40021185849
  • Peer Reviewed
• [Journal Article] Double-flap technique as an antireflux procedure in esophagogastrostomy after proximal gastrectomy (2016)
  • Author(s): Kuroda S, Nishizaki M, Kikuchi S, Noma K, Tanabe S, Kagawa S, Shirakawa Y, Fujiwara T
  • Journal Title: J Am Coll Surg Volume: 223 Issue: 2 Pages: e7-e13
  • DOI: 10.1016/j.jamcollsurg.2016.04.041
  • Peer Reviewed
• [Presentation] Tumor associated macrophages promote malignant phenotypes of disseminated human gastric cancer cells in intraperitoneal cancer immune microenvironment (2017)
  • Author(s): Shuichi Sakamoto, Shunsuke Kagawa, Kazuya Kuwada, Atene Ito, Tetsuya Kagawa, Satoru Kikuchi, Shinji Kuroda, Ryuichi Yoshida, Hiroshi Tazawa, Toshiyoshi Fujiwara
  • Organizer: American Association for Cancer Research, Annual Meeting 2017
  • Place of Presentation: ワシントンDC, 米国
  • Year and Date: 2017-04-01
  • Int'l Joint Research
• [Presentation] 蛍光ウイルスによる腹腔内の腫瘍関連マクロファージと膵癌細胞の関連性の解析 (2016)
  • Author(s): 桑田 和也, 香川 俊輔, 坂本 修一, 渡邉 めぐみ, 香川 哲也, 菊地 覚次, 黒田 新士, 吉田 龍一, 浦田 泰生, 田澤 大, 藤原 俊義
  • Organizer: 第75回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-06
• [Presentation] Virus-guided fluorescent imaging of pancreatic cancer cells in the peritoneal cavity for an insight into roles of tumor-associated macrophage (2016)
  • Author(s): Kazuya Kuwada, Shunsuke Kagawa, Megumi Watanabe, Shuichi Sakamoto, Tetsuya Kagawa, Satoru Kikuchi, Shinji Kuroda, Ryuichi Yoshida, Hiroshi Tazawa and Toshiyoshi Fujiwara.
  • Organizer: The 22nd Annual Meeting of Japan Society of Gene and Cell Therapy
  • Place of Presentation: 虎ノ門ヒルズフォーラム（東京都港区）
  • Year and Date: 2016-07-28
  • Int'l Joint Research
• [Presentation] Intraperitoneal macrophages in patients with gastric cancer are polarized to promote malignant phenotypes of disseminated cancer cells. (2016)
  • Author(s): 渡辺 めぐみ, 香川 俊輔, 桒田 和也, 坂本 修一, 菊地 覚次, 黒田 新士, 岸本 浩行, 西崎 正彦, 田澤 大, 藤原 俊義
  • Organizer: 第71回 日本消化器外科学会
  • Place of Presentation: あわぎんホール（徳島県徳島市）
  • Year and Date: 2016-07-14
• [Presentation] Clinical implications of fluorescence-emitting virus guided peritoneal cytology in gastrointestinal cancer. (2016)
  • Author(s): Kagawa S, Watanabe M, Kuwata K, Sakamoto S, Shigeyasu K, Tazawa H, Kuroda S, Kikuchi S, Yoshida R, Nishizaki M, Kishimoto H, Nagasaka T, Fujiwara T.
  • Organizer: The 19th International Congress of Cytology: ICC2016
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-05-28
  • Int'l Joint Research / Invited
• [Presentation] Clinical implications of fluorescence-emitting virus guided peritoneal cytology in gastrointestinal cancer. (2016)
  • Author(s): 香川俊輔、渡邉めぐみ、桒田和也、他
  • Organizer: 19th International Congress of Cytology
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-05-28
  • Int'l Joint Research / Invited
• [Presentation] Functional analysis of tumor-associated macrophage utilizing virus-guided fluorescent imaging of pancreatic cancer cells in the peritoneal cavity (2016)
  • Author(s): 桒田和也、香川俊輔、他
  • Organizer: the 107th Annual Meeting of American Association for Cancer Research 2016
  • Place of Presentation: 米国 ニューオリンズ
  • Year and Date: 2016-04-17
  • Int'l Joint Research
• [Presentation] Fluorescence-guided imaging of gastric cancer cells for an insight into peritoneal dissemination (2016)
  • Author(s): 香川俊輔、渡邉めぐみ、桒田和也、他
  • Organizer: 第88回日本胃癌学会総会
  • Place of Presentation: 大分県別府市
  • Year and Date: 2016-03-17