Selective pressure driving cancer cell fate decisions: the mechanism of the creation

• Project/Area Number: 23590478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kyoto Sangyo University
• Principal Investigator: ITANO Naoki 京都産業大学, 総合生命科学部, 教授 (40257712)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: がん微小環境 / ヒアルロン酸 / がん幹細胞 / 淘汰圧 / マクロファージ / 糖鎖 / 癌 / 微小環境 / 幹細胞 / 炎症

Research Abstract

In this study, we have investigated the mechanisms of cancer stem cell (CSC) enrichment under the selective pressure and the way in which CSCs can escape from this pressure. Flow cytometric analysis indicated the enrichment of CSC-like cells in hyaluronan synthase 2 (Has2)-overexpressing cancer cells. We also found that Has2 overexpressing cells produced significantly higher levels of TNF-alpha and TGF-beta than the control cells. Taken together, our findings provided a novel idea that CSCs can create selective pressure via the macrophage activation induced by up-regulating TNF-alpha in a hyaluronan-dependent manner. We further suggest that the anti-tumor immune action of TGF-beta allows cancer cells to escape from the selective pressure.

Research Products

• [Journal Article] -糖鎖と疾患‐癌進展におけるヒアルロン酸腫瘍微小環境の役割 (2013)
  • Author(s): 望月信利,板野直樹
  • Journal Title: 病理と臨床 Volume: 31 Pages: 875-882
• [Journal Article] Crucial role of hyaluronan in neointimal formation after vascular injury (2013)
  • Author(s): Kashima, Y., Takahashi, M., Shiba, Y., Itano, N., Izawa, A., Koyama, J., Nakayama, J., Taniguchi, S., Kimata, K., and Ikeda, U.
  • Journal Title: PLoS One Volume: 8(3)
• [Journal Article] －糖鎖と疾患－ 癌進展におけるヒアルロン酸腫瘍微小環境の役割 (2013)
  • Author(s): 望月信利，板野直樹
  • Journal Title: 病理と臨床 Volume: 31 Pages: 875-882
• [Journal Article] Hyaluronan expressed by the hematopoietic microenvironment is required for bone marrow hematopoiesis (2012)
  • Author(s): Goncharova, V., Serobyan, N., Iizuka, S., Schraufstatter, I., de Ridder, A., Povaliy, T., Wacker, V., Itano, N., Kimata, K., Orlovskaja, I.A., Yamaguchi, Y., and Khaldoyanidi, S.
  • Journal Title: J. Biol. Chem Volume: 287(30) Pages: 25419-25433
• [Journal Article] Restriction of mast cell proliferation through hyaluronan synthesis by co-cultured fibroblasts (2012)
  • Author(s): Takano, H., Nakazawa, S., Shirata, N., Tamba, S., Furuta, K., Tsuchiya, S., Morimoto, K., Itano, N., Irie, A., Ichikawa, A., Kimata, K., Nakayama, K., Sugimoto, Y., and Tanaka, S.
  • Journal Title: Biol. Pharm. Bull Volume: 35(3) Pages: 408-412
  • NAID: 130001872324
• [Journal Article] Enhanced inflammation and accelerated wound closure following tetraphorbol ester application or full-thickness wounding in mice lacking hyaluronan synthases Has1 and Has3 (2012)
  • Author(s): Mack, J.A., Feldman, R.J., Itano, N., Kimata, K., Lauer, M., Hascall, V.C., and Maytin, E.V.
  • Journal Title: J. Invest. Dermatol Volume: 132(1) Pages: 198-207
• [Journal Article] Enhanced inflammation and accelerated wound closure following tetraphorbol ester application or full-thickness wounding in mice lacking hyaluronan synthases Has1 and Has3. (2012)
  • Author(s): Mack JA, Feldman RJ, Itano N, Kimata K, Lauer M, Hascall VC, Maytin EV.
  • Journal Title: J Invest Dermatol. Volume: 132 Issue: 1 Pages: 198-207
  • DOI: 10.1038/jid.2011.248
  • Peer Reviewed
• [Journal Article] Inflammatory alterations of the extracellular matrix in the tumor microenvironment. (2011)
  • Author(s): J. Iijima, K. Konno, and N. Itano
  • Journal Title: Cancers Volume: 3 Pages: 3189-3205
  • Peer Reviewed
• [Presentation] ヒアルロン酸合成異常と癌の進展 (2013)
  • Author(s): 板野直樹
  • Organizer: 第32回日本糖質学会年会
  • Place of Presentation: 大阪市(シンポジウム)
  • Year and Date: 2013-08-06
• [Presentation] Hyperproduction of hyaluronan generate cancer stem-like cells (2013)
  • Author(s): Chanmee, T., Konno, K., Kongtawelert, P., Itano, N.
  • Organizer: International Society for Hyaluronan Sciences 9th International Conference (Hyaluronan 2013)
  • Place of Presentation: Oklahoma City, OK, USA
  • Year and Date: 2013-07-07
• [Presentation] Impact of the hyaluronan-rich tumor microenvironment on cancer progression (2013)
  • Author(s): Itano, N.
  • Organizer: International Society for Hyaluronan Sciences 9th International Conference (Hyaluronan 2013)
  • Place of Presentation: Oklahoma City, OK, USA
  • Year and Date: 2013-07-06
• [Presentation] ヒアルロン酸腫瘍微小環境の形成と癌の進展 (2012)
  • Author(s): 板野直樹
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-28
• [Presentation] 腫瘍関連マクロファージとヒアルロン酸リッチ腫瘍微小環境 (2011)
  • Author(s): 板野直樹
  • Organizer: 北海道大学遺伝子病制御研究所共同研究集会(招待講演)
  • Place of Presentation: 札幌市
• [Presentation] Impact of the hyaluronan-rich tumor microenvironment on cancer progression. (2011)
  • Author(s): Naoki Itano
  • Organizer: Uppsala University Svedberg Seminar Series(招待講演)
  • Place of Presentation: Uppsala, Sweden
• [Presentation] ヒアルロン酸合成異常と癌の進展 (2011)
  • Author(s): 板野直樹
  • Organizer: 第8回日本病理学会カンファレンス(招待講演)
  • Place of Presentation: 松本市
• [Presentation] Impact of the hyaluronan-rich tumor microenvironment on cancer progression
  • Author(s): N. Itano
  • Organizer: International Society for Hyaluronan Sciences 9th International Conference
  • Place of Presentation: Oklahoma City, OK, USA
  • Invited
• [Presentation] Hyperproduction of hyaluronan generate cancer stem-like cells
  • Author(s): T. Chanmee, K. Konno, P. Kongtawelert, N. Itano
  • Organizer: International Society for Hyaluronan Sciences 9th International Conference
  • Place of Presentation: Oklahoma City, OK, USA
• [Presentation] Hyaluronan production regulates self-renewal of cancer stem cells
  • Author(s): T. Chanmee, N. Itano
  • Organizer: 第22回日本がん転移学会学術集会・総会
  • Place of Presentation: 松本市
• [Presentation] ヒアルロン酸合成異常と癌の進展
  • Author(s): 板野直樹
  • Organizer: 第32回日本糖質学会年会
  • Place of Presentation: 大阪市
• [Remarks]
  • URL: http://www.cc.kyoto-su.ac.jp/~itanon/index2.html