Roles of MFG-E8 on oral squamous cell carinoma

• Project/Area Number: 23659948
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kochi University
• Principal Investigator: KITAMURA NAOYA 高知大学, 教育研究部医療学系, 助教 (70351921)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Tetsuya 高知大学, 教育研究部医療学系, 教授 (00200824) ; SASABE Eri 高知大学, 教育研究部医療学系, 助教 (40363288) ; YOSHIMURA Tomohide 高知大学, 教育研究部医療学系, 助教 (80452697) ; RI Yasuhiro 高知大学, 教育研究部医療学系, 助教 (70587526) ; OHNO Seiji 高知大学, 教育研究部医療学系, 助教 (40624995)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: MFG-E8 / 口腔扁平上皮癌 / LAK細胞

Research Abstract

The milk fat globule factor-E8 (MFG-E8), a major component of the milk fat globule membrane, is assumed to be involved in various developmental and homeostatic processes in addition to the eat-me signal generation. Here, we investigated MFG-E8 involvement in OSCC cell susceptibility to chemoradioimmunotherapy. Irradiation and not chemotherapeutic drugs induced MFG-E8 secretion from an OSCC cell line. LAK cells caused greater impairment of OSC-6 cells (strongly expressing MFG-E8) than OSC-3 cells (weakly expressing MFG-E8). Furthermore, in OSC-6 cells, LAK cell-mediated cytotoxicity was enhanced on pretreatment with r-rays. In irradiated OSC-6 cells, the enhanced LAK cell-mediated cytotoxicity was suppressed by transfection with MFG-E8 siRNA. The susceptibility of OSC-3 and OSC-6 cells to 5-FU and CDDP remained unaffected on transfection with MFG-E8 siRNA. These results suggest that MFG-E8 increases the OSCC cell susceptibility to LAK cells and acts as a bridging molecule.