Cell motility of repopulated tumor cells after radiotherapy

• Project/Area Number: 20790872
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Hokkaido University
• Principal Investigator: TSUTSUMI Kaori Hokkaido University, 大学院・保健科学研究院, 助教 (80344505)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 放射線治療 / 再増殖腫瘍細胞 / マトリックスメタロプロテアーゼ / インテグリン / 細胞運動 / 細胞接着分子 / 接着斑 / 浸潤

Research Abstract

Radiotherapy is an important noninvasive treatment for many types of cancer. Recently, remarkable progress of technology of radiotherapy leads to an improvement of local control rate. However, the emergence of tolerant cells during or after radiotherapy remains problematic. The patients who relapsed by repopulated tumor have worse prognoses because of more malignant character of repopulated tumor compared with that of before irradiation. Unfortunately, the molecular mechanisms of cause for tumor repopulation remain unknown. To elucidate the molecular profile of repopulated tumor, present study analyzed the cellular properties of surviving tumor after X-ray irradiation by using IR cells which is the model cell line of repopulated tumor. The mRNA expression levels of matrix metalloproteinases (MMPs) were upregulated in IR cells compared with parental cells. IR cells possessed high gelatinase activities, and increased cell motility, and more invasiveness than parental cells on type-I collagen-coated well. However, phosphorylation of EGF receptor and ERK and cell growth were the same levels between parental cells and IR cells. On the other hand, IR cells adhered more tightly to collagen-coated dishes than parental cells. Consistently, integrin β1, paxillin, and phosphorylated FAK, that were cell-substrate adhesion molecules, were strongly localized at focal adhesions in IR cells, as visualized by immunofluorescence. Whereas, the expression levels of these adhesion molecules were not different between parental cells and IR cells. Increased invasion, migration, and adhesion in IR cells after irradiation might result from the differences of localization of focal adhesion molecules in the cells. These molecules may be important therapeutic targets for the control of repopulated tumors after radiotherapy.

Research Products

• [Journal Article] Increased motility and invasiveness in tumor cells that survive 10 Gy irradiation. (2009)
  • Author(s): Tsutsumi K, Tsuda M, Yazawa N, Nakamura H, Ishihara S, Haga H, Yasuda M, Yamazaki R, Shirato H, Kawaguchi H, Nishioka T, Ohba Y
  • Journal Title: Cell Struct Funct 34(2) Pages: 89-96
  • Peer Reviewed
• [Journal Article] Increased motility and invasiveness in tumor cells that survive 10 Gyirradiation (2009)
  • Author(s): Kaori Tsutsumi
  • Journal Title: Cell Structure and Function 34 Pages: 89-96
  • Peer Reviewed
• [Presentation] Cell Motility And Invasion Of Surviving Tumor Cells After 10 Gy Irradiation. (2009)
  • Author(s): Tsutsumi K, Tsuda M, Yazawa N, Nakamura H, Yasuda M, Yamazaki R, Shirato H, Kawaguchi H, Ohba Y, Nishioka T
  • Organizer: 51st ASTRO Annual Meeting
  • Place of Presentation: Chicago, USA
• [Presentation] Cell Motility And Invasion Of Surviving Tumor Cells After 10 Gy Irradiation (2009)
  • Author(s): Kaori Tsutsumi
  • Organizer: 51st ASTRO Annual Meeting
  • Place of Presentation: Chicago, USA
• [Presentation] Visualization of an interaction between Ras and Ras-binding domain in living cells by bimolecular fluorescence complementation (2008)
  • Author(s): 堤香織
  • Organizer: Experimental Biology 2008
  • Place of Presentation: San Diego Convention Center(アメリカ、 サンディエゴ)
  • Year and Date: 2008-04-06