The significance of macrophage in tumor microenveironment

• Project/Area Number: 21790388
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Kumamoto University
• Principal Investigator: KOMOHARA Yoshihiro Kumamoto University, 大学院・生命科学研究部, 助教 (40449921)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: マクロファージ / M2 / 腎がん / CD163 / CD204 / 腫瘍関連マクロファージ / TAM / スカベンジャー受容体 / がん

Research Abstract

In this study, we demonstrated the significance of macrophage in development of tumor microenvironment. We found that high infiltration of CD163- and CD204-positive M2 macrophages correlate to poor clinical prognosis in patients with glioma, cholangiocellular carcinoma, ovarian cancer, malignant lymphoma, and kidney cancer. By means of using murine cancer model, we showed that CD204 regulates the macrophage activation, differentiation to M2 phenotype, and promotes the tumor development. By analysis using human pathological specimens, we interestingly suggested the significant role of CD163 in development of tumor microenvironment.

Research Products

• [Journal Article] Corosolic acid inhibits glioblastoma cell proliferation by suppressing the activation of STAT3 and NF-κB in tumor cells and tumor-associated macrophages. (2011)
  • Author(s): Fujiwara Y, Komohara Y, Ikeda T, Takeya M.
  • Journal Title: Cancer Sci 102 Pages: 206-211
  • Peer Reviewed
• [Journal Article] Involvement of M2-polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation. (2010)
  • Author(s): Takaishi K, Komohara Y, Tashiro H, Ohtake H, Nakagawa T, Katabuchi H, Takeya M.
  • Journal Title: Cancer Sci 101 Pages: 2128-2136
  • NAID: 10027832147
  • Peer Reviewed
• [Journal Article] Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma. (2010)
  • Author(s): Hasita H, Komohara Y, Okabe H, Masuda T, Ohnishi K, Lei XF, Beppu T, Baba H, Takeya M.
  • Journal Title: Cancer Sci Equal contributor 101 Pages: 1913-1919
  • NAID: 10027831002
  • Peer Reviewed
• [Journal Article] Ratio of M2 macrophage expression in closely associated with poor prognosis for Angioimmunoblastic T-cell lymphoma (AILT). (2010)
  • Author(s): Niino D, Komohara Y, Murayama T, Aoki R, Kimura Y, Hashikawa K, Kiyasu J, Takeuchi M, Seufuji N, Sugita Y, Takeya M, Ohshima K.
  • Journal Title: Pathol Int 60 Pages: 278-283
  • Peer Reviewed
• [Journal Article] Macrophages in Langerhans cell histiocytosis are differentiated toward M2 phenotype-their possible involvement in pathological process. (2010)
  • Author(s): Ohnishi K, Komohara Y, Sakashita N, Iyama K, Murayama T, Takeya M.
  • Journal Title: Pathol Int 60 Pages: 27-34
  • NAID: 10027382665
  • Peer Reviewed
• [Journal Article] Significance of alternatively activated macrophages in patients with intrahepatic cholangiocar cinoma. (2010)
  • Author(s): Hasita H, Komohara Y, et al
  • Journal Title: Cancer Science Volume: 101 Pages: 1913-1919
  • NAID: 10027831002
  • Peer Reviewed
• [Journal Article] Involvement of M2-polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation (2010)
  • Author(s): Takaishi K, Komohara Y, et al
  • Journal Title: Cancer Science Volume: 101 Pages: 2128-2136
  • NAID: 10027832147
  • Peer Reviewed
• [Journal Article] Ratio of M2 macrophage expression in closely associated with poor prognosis for Angioimmunoblastic T-cell lymphoma (AILT) (2010)
  • Author(s): Niino D, Komohara Y, et al
  • Journal Title: Pathology International Volume: 60 Pages: 278-283
  • Peer Reviewed
• [Journal Article] Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to up-regulation of nitric oxide and IFN-gamma production by tumor-associated macrophages. (2009)
  • Author(s): Komohara Y, Takemura K, Lei XF, Sakashita N, Harada M, Suzuki H, Kodama T, Takeya M.
  • Journal Title: Cancer Sci 100 Pages: 2160-2165
  • Peer Reviewed
• [Journal Article] Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors. (2009)
  • Author(s): Kawamura K, Komohara Y, Takaishi K, Katabuchi H, Takeya M.
  • Journal Title: Pathol Int Equal contributor. 59 Pages: 300-305
  • NAID: 10027380027
  • Peer Reviewed
• [Journal Article] Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to up-regulation of nitric oxide and IFN-gamma production by tumor-associated macrophages. (2009)
  • Author(s): Komohara Y, et al.
  • Journal Title: Cancer Science 100 Pages: 2160-2165
  • Peer Reviewed
• [Journal Article] Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors. (2009)
  • Author(s): Kawamura K, Komohara Y, et al
  • Journal Title: Pathology International 59 Pages: 300-305
  • NAID: 10027380027
  • Peer Reviewed
• [Journal Article] Decreased expression of germinal center-associated nuclear protein is involved in chromosomal instability in malignant gliomas. (2009)
  • Author(s): Ohta K, Komohara Y, et al.
  • Journal Title: Cancer Science 100 Pages: 2069-2076
  • NAID: 10027196786
  • Peer Reviewed
• [Presentation] The significance of anti-inflammatory (M2) macrophages and its prognostic relevance in clear cell renal cell carcinoma.(国際ポスターセッション) (2010)
  • Author(s): Yoshihiro Komohara, Horlad Hasita, Koji Ohnishi, Yasuo Fujiwara, Motohiro Takeya
  • Organizer: 第56回日本病理学会秋期特別総会
  • Place of Presentation: 小倉、西日本総合展示場
• [Presentation] 竹屋元裕腎淡明細胞癌におけるM2マクロファージの役割と臨床予後との関連性 (2010)
  • Author(s): 菰原義弘、Horlad Hasita、大西紘二、藤原章雄
  • Organizer: 第7回日本病理学会カンファレンス
  • Place of Presentation: 岡山、岡山コンベンションセンター
• [Presentation] 竹屋元裕脳原発悪性リンパ腫におけるマクロファージ浸潤と臨床予後に関する解析 (2010)
  • Author(s): 菰原義弘、大西紘二
  • Organizer: 第50回日本リンパ網内系学会
  • Place of Presentation: 新潟、朱鷺メッセ
• [Presentation] Stat3を介したグリオーマ細胞とマクロファージの細胞間相互作用 (2010)
  • Author(s): 菰原義弘、藤原章雄、大西紘二、HasitaHorlad、竹屋元裕
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京、京王ホテル
• [Presentation] 腎淡明細胞癌におけるM2マクロファージの役割と臨床予後との関連性 (2010)
  • Author(s): 菰原義弘
  • Organizer: 第7回日本病理学会カンファレンス
  • Place of Presentation: 岡山市(岡山コンベンションセンター)
• [Presentation] 腫瘍内浸潤マクロファージにおけるCD204(class A scavenger receptor)発現の意義 (2009)
  • Author(s): 菰原義弘
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都・国際会議場
  • Year and Date: 2009-05-01
• [Presentation] Stat3 mediates the cell-cell interaction of macrophages and tumor cells in human glioblastoma. (2009)
  • Author(s): Yoshihiro Komohara, Yukio Fujiwara, Motohiro Takeya
  • Organizer: 17th International Synposium on Molecular Cell Biology of Macrophages.
  • Place of Presentation: Kanazawa, Japan、KKR金沢ホテル
• [Presentation] 竹屋元裕腫瘍内浸潤マクロファージにおけるCD204(class A scavenger receptor)発現の意義 (2009)
  • Author(s): 菰原義弘、竹村健一、坂下直実
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都:国際会議場
• [Remarks] ホームページ等
  • URL: http://www.medic.kumamoto-u.ac.jp/dept/patho2/pages/komohara.html
• [Remarks]
  • URL: http://www.medic.kumamoto-u.ac.jp/dept/patho2/pages/komohara.html