The significance of cell-cell interaction between macrophages and cancer cells in tumor development

• Project/Area Number: 23790407
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Kumamoto University
• Principal Investigator: KOMOHARA Yoshihiro 熊本大学, 大学院・生命科学研究部, 講師 (40449921)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 分子病理 / 癌 / マクロファージ / 細胞間相互作用 / グリオーマ / ATLL

Research Abstract

In this study , we investigated the significance of tumor-associated macrophages (TAM) inhuman malignant tumors including glioma and adult T cell lymphoma/leukemia (ATLL).As the result of immunostaining, many TAMs were detected in tumor tissues and highnumber of CD163-positive TAMs was well associated to worse clinical prognosis in gliomaand ATLL. By means of in vitro coculture study , we found glioma cells and ATLL cells weresignificantly activated by coculture with M2 macrophages. Direct cell-cell contact wasimportant in tumor cell activation. Direct contact with tumor cells induced significantmacrophage activation and which in turn soluble factors from macrophages stimulatedtumor cells. Soluble factors such as C5a、TNF-a、GRO-a,IL-6、I-309 were secreted fromactivated macrophages. In glima, membrane type M-CSF on tumor cell surface couldstimulate macrophage activation strongly . In ATLL, detail mechanisms have never beenuncovered but CD163 is considered to be involved in cell-cell interaction.

Research Products

• [Journal Article] Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells (2013)
  • Author(s): Horlad Hasita, Fujiwara Yukio, Takemura Kenichi, Ohnishi Koji, Ikeda Tsuyoshi, Tsukamoto Hirotake, Mizuta Hiroshi, Nishimura Yasuharu, Takeya Motohiro, Komohara Yoshihiro
  • Journal Title: Mol. Nutri. Food Res Volume: 57 (6) Issue: 6 Pages: 1-9
  • DOI: 10.1002/mnfr.201200610
  • Peer Reviewed
• [Journal Article] Possible involvement of signal transducer and activator of transcription-3 in cell-cell interactions of peritoneal macrophages and endometrial stromal cells in human endometriosis. (2013)
  • Author(s): Itoh F, Komohara Y, Takaishi K, Honda R, Tashiro H, Kyo S, Katabuchi H, Takeya M
  • Journal Title: Fertil Steril Volume: 99 Issue: 6 Pages: 1705-1713
  • DOI: 10.1016/j.fertnstert.2013.01.133
  • Peer Reviewed
• [Journal Article] Importance of direct macrophage-tumor cell interaction on progression of human glioma (2012)
  • Author(s): Komohara Y, Horlad H, Ohnishi K, Fujiwara Y , Bai B, Nakagawa T, Suzu S, Nakamura H,Kuratsu J, Takeya M
  • Journal Title: Cancer Sci Volume: 103 Pages: 2165-2172
  • Peer Reviewed
• [Journal Article] Importance of direct macrophage-tumor cell interaction on progression of human glioma. (2012)
  • Author(s): Komohara Y, Horlad H, Ohnishi K, Fujiwara Y, Bai B, Nakagawa T, Suzu S, Nakamura H, Kuratsu J, Takeya M.
  • Journal Title: Cancer Sci Volume: 103(12) Issue: 12 Pages: 2165-72
  • DOI: 10.1111/cas.12015
  • Peer Reviewed
• [Journal Article] Macrophage infiltration and its prognostic relevance in clear renal cell carcinoma. (2011)
  • Author(s): Komohara Y, Hasita H, Ohnishi K, Fujiwara Y, Suzu S, Eto M, Takeya M.
  • Journal Title: Cancer Sci Volume: 102 Pages: 1424-1431
  • Peer Reviewed
• [Journal Article] M2 macrophage/microglial cells induce activation of Stat3 in primary central nervous system lymphoma (2011)
  • Author(s): Komohara Y, Horlad H, Ohnishi K, Ohta K, Makino K, Hondo H, Yamanaka R, Kajiwara K, Saito T, Kuratsu J, Takeya M.
  • Journal Title: J Clin Exp Hematol Volume: 51 Pages: 93-99
  • NAID: 10030207599
  • Peer Reviewed
• [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 Volume: 102 Pages: 206-211
  • Peer Reviewed
• [Journal Article] Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells
  • Author(s): Horlad H, Fujiwara Y , Takemura K, OhnishiK, Ikeda T, Tsukamoto H, Mizuta H,Nishimura Y , Takeya M, Komohara Y(**)
  • Journal Title: Mol Nutr Food Res (In press) **: corresponding author
  • Peer Reviewed
• [Journal Article] Possible involvement of Stat3 in cell-cell interaction between peritoneal macrophages and endometrial stromal cells in human endometriosis
  • Author(s): Itoh F , Komohara Y(*,**), Takaishi K,Honda R, Tashiro H, Kyo S, Katabuchi H,Takeya M
  • Journal Title: Fertil Steril (in press) * : Equal contributor . **: corresponding author
  • Peer Reviewed
• [Presentation] 子宮内膜症の発生・進展における腹腔マクロファージの役割 (2012)
  • Author(s): 菰原義弘、伊藤史子、大西紘二、藤原章雄、竹屋元裕
  • Organizer: 第101回 日本病理学会総会
  • Place of Presentation: 東京、京王プラザ
• [Presentation] Alternatively activated (M2) macrophages induce activation of Stat3 in primary central nervous system lymphoma (2012)
  • Author(s): Yoshihiro Komohara, Koji Ohnishi, Motohiro Takeya
  • Organizer: The 11^th Korean-Japanese lymphoreticular workshop
  • Place of Presentation: Seoul, Korea
• [Presentation] 子宮内膜症の発生・進展における腹腔マクロファージの役割. (2012)
  • Author(s): 菰原義弘
  • Organizer: 第101回 日本病理学会総会
  • Place of Presentation: 東京、京王プラザホテル
• [Presentation] さまざまな悪性腫瘍における腫瘍関連マクロファージの分化・活性化状態と病態への関与 (2012)
  • Author(s): 菰原義弘
  • Organizer: 第52回 日本リンパ網内系学会総会
  • Place of Presentation: 福島、福島ビューホテル
  • Invited
• [Presentation] ヒト腫瘍組織における M2 マクロファージの役割-Stat3 に注目した腫瘍細胞との細胞間相互作用について (2011)
  • Author(s): 菰原義弘、Horlad Hasita、大西紘二、藤原章雄、竹屋元裕
  • Organizer: 第51回 日本リンパ網内系学会
  • Place of Presentation: 福岡、福岡国際会議場
• [Presentation] The significance of anti-inflammatory (M2) macrophages in clear cell renal cell carcinoma. (2011)
  • Author(s): Komohara Y, Hasita H, Ohnishi K, Fujiwara Y, Takeya M
  • Organizer: 19th International Synposium on Molecular Cell Biology of Macrophages.
  • Place of Presentation: Osaka, Japan, ANA Gate Tower Hotel
• [Presentation] グリオーマ細胞とマクロファージの細胞間相互作用には直接接着が必要である
  • Author(s): 菰原義弘、ハスタ、大西紘二、藤原章雄、竹屋元裕
  • Organizer: 第100回 日本病理学会総会
  • Place of Presentation: 横浜、パシフィコ横浜
• [Presentation] ヒト腫瘍組織におけるM2マクロファージの役割―Stat3に注目した腫瘍細胞との細胞間相互作用について
  • Author(s): 菰原義弘、Horlad Hasita、大西紘二、藤原章雄、竹屋元裕
  • Organizer: 第51回 日本リンパ網内系学会
  • Place of Presentation: 福岡、福岡国際会議場
• [Remarks] ホームページ
  • URL: http://srv02.medic.kumamoto-u.ac.jp/dept/patho2/pages/komohara.html
• [Remarks] 菰原義弘 研究内容
  • URL: http://srv02.medic.kumamoto-u.ac.jp/dept/patho2/pages/komohara.html
• [Remarks]
  • URL: http://www.medic.kumamoto-u.ac.jp/dept/patho2/patho2.html