CD44-targetted therapy for CD44-high expressing tumors by ultra-low-molecular-weight hyaluronan
| Project/Area Number |
25461585
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | University of Yamanashi |
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Principal Investigator |
SUGITA Kanji 山梨大学, 総合研究部, 教授 (60138055)
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| Co-Investigator(Renkei-kenkyūsha) |
INUKAI Takeshi 山梨大学, 総合研究部, 准教授 (30293450)
GOI Kumiko 山梨大学, 総合研究部, 講師 (70324192)
OSHIRO Hiroko 山梨大学, 総合研究部, 助教 (50377537)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 超低分子量ヒアルロン酸 / 白血病 / CD44 / 細胞死 / ネクローシス / ヒアルロン酸 / ALL |
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| Outline of Final Research Achievements |
We investigated the biological effects of ultra-low-molecular-weight (ULMW)-HA on MLL+ALL cell lines with high surface expression of CD44, and found that the addition of ULMW-HA strongly suppressed thymidine uptakes. The cell line almost lacking surface CD44 expression established by genome editing using CRISPR/Cas9 system showed no suppression, demonstrating an essential role of surface CD44 expression for ULMW-HA-triggered inhibition of thymidine uptake. This inhibition was not due to cell cycle arrest but due to induction of cell death. The cell death was neither blocked by pan-caspase inhibitor Z-VAD-FMK nor autophagy inhibitor 3-methyladenine, but was completely blocked by necrosis inhibitor necrostatin-1. ULMW-HA-triggered necrotic cell death was further supported by morphological changes on transmission electron microscopy. Elevation of intracellular reactive oxygen species production after ULMW-HA stimulation suggested a role for inducting this necrotic cell death.
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Report
(4 results)
Research Products
(2 results)
