The function of intraperitoneal macrophage and its tumorigenesis in gastic cancer with peritoneal metastasis

• Project/Area Number: 25462015
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kanazawa University
• Principal Investigator: Fushida Sachio 金沢大学, 医学系, 准教授 (10301194)
• Co-Investigator(Kenkyū-buntansha): HARADA SHINICHI 金沢大学, 医学系, 助教 (90272955)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 胃癌 / 腹膜播種 / 腫瘍浸潤マクロファージ / 線維化 / α1酸性糖蛋白 / パクリタキセル / エリスロマイシン / 癌微小環境 / 腫瘍関連マクロファージ / 胃癌腹膜播種 / 癌性腹水 / α1-酸性糖蛋白 (AGP) / TLR4 / α１酸性糖蛋白 (AGP)

Outline of Final Research Achievements

First, we investigated whether M2 macrophages participate in the development of peritoneal carcinomatosis (PC) in gastric cancer.The number of peritoneal macrophages with the M2 phenotype was significantly higher in gastric cancer patients with PC. the coexistence of MKN45 cells with M2 macrophages resulted in cancer cell proliferation and an acceleration of tumor growth in the xenograft model.
Second, increased concentrations of α1-acid glycoprotein (AGP), an important drug-binding protein, have been reported in the plasma and ascites of cancer patients. This study sought to clarify whether AGP binds to PTX and alters its anticancer effects. AGP > 400 μg/mL significantly suppressed the cell growth inhibitory effect of PTX in vitro, but the co-administration of EM restored it. Elevated AGP concentrations were observed in the ascites of PC model mice. Administration of PTX alone did not markedly diminish PC, whereas co-administration of PTX and EM significantly reduced PC.

Research Products

• [Journal Article] Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination. (2015)
  • Author(s): Yamaguchi T, Fushida S, Yamamoto Y, Tsukada T, Kinoshita J, Oyama K, Miyashita T, Tajima H, Ninomiya I, Munesue S, Harashima A, Harada S, Yamamoto H, Ohta T.
  • Journal Title: Gastric Cancer Volume: 18 Issue: 4 Pages: 1-14
  • DOI: 10.1007/s10120-015-0579-8
  • NAID: 40020959187
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elevated alpha1-acid glycoprotein in gastric cancer patients inhibits the anticancer effects of paclitaxel, effects restored by co-administration of erythromycin (2015)
  • Author(s): Ｏｈｂａｔａｋｅ Ｙ， Ｆｕｓｈｉｄａ Ｓ， ｅｔ ａｌ．
  • Journal Title: Ｃｌｉｎｉｃａｌ ａｎｄ ｅｘｐｅｒｉｍｅｎｔａｌ ｍｅｄｉｃｉｎｅ Volume: Ｅｐｕｂ ａｈｅａｄ ｏｆ ｐｒｉｎｔ Issue: 4 Pages: 1-8
  • DOI: 10.1007/s10238-015-0387-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Bidirectional communication between gastric cancer cells and macrophages (2014)
  • Author(s): 山口貴久
  • Organizer: 第25回日本消化器癌発生学会総会
  • Place of Presentation: ホテル日航福岡（福岡市）
  • Year and Date: 2014-11-13 – 2014-11-14
• [Presentation] 腹膜播種における胃癌細胞とマクロファージの形質転換 (2014)
  • Author(s): 山口貴久
  • Organizer: 第８６回日本胃癌学会総会
  • Place of Presentation: パシフィコ横浜(横浜市)
• [Presentation] α１ー酸性タンパク質によるパクリタキセルの活性阻害とエリスロマイシン併用療法による再活性化 (2013)
  • Author(s): 大畠慶直
  • Organizer: 第22回日本がん転移学会学術集会総会
  • Place of Presentation: ホテルブエナビスタ松本(松本市)