| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Research Abstract |
CD44 is a cell surface receptor for hyaluronan and is implicated in cancer invasion and metastasis. Proteolytic cleavage of CD44 plays a critical role in the migration of cancer cells and is regulated by factors present in the tumor microenvironment, such as hyaluronan oligosaccharides and epidermal growth factor. However, molecular mechanisms underlying the proteolytic cleavage on membranes remain poorly understood. In this study, we demonstrated that cholesterol depletion with methyl-・-cyclodextrin, which disintegrates membrane lipid rafts, enhances CD44 shedding mediated by a disintegrin and metalloproteinase 10(ADAM10), and that cholesterol depletion disorderes CD44 localization to the lipid raft. We also evaluated the effect of long-term cholesterol reduction using a statin agent, and demonstrated that statin enhances CD44 shedding and suppresses cancer cell migration on a hyaluronan-coated substrate. Our results indicate that membrane lipid organization regulates CD44 shedding, and propose a possible molecular mechanism by which cholesterol reduction might be effective for preventing and treating the cancer progression.
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