| Budget Amount *help |
¥70,200,000 (Direct Cost: ¥54,000,000、Indirect Cost: ¥16,200,000)
Fiscal Year 2014: ¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000)
Fiscal Year 2013: ¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000)
Fiscal Year 2012: ¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000)
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| Outline of Final Research Achievements |
Lymphatic vasculature forms a network of vessels that drain interstitial fluid from tissues and return this fluid to the blood. Lymphangiogesis, the formation of lymphatic vessels from preexisting lymphatic vessels, plays an important role in homeostasis of interstitial fluids and immunity. We found that lymphangiogenesis in chronic inflammation and secondary lymphedema was regulated by COX-2. The lymphatic system is an important route for cancer dissemination, and lymph node metastasis (LNM) serves as a critical prognostic determinant in cancer patients. We clarified contribution of COX-2-derived PGE2 in formation of a premetastatic niche and LNM. Stromal cell-derived factor-1 (SDF-1) was elevated in DCs before LLC cell infiltration to lymph nodes, and was important to form premetastatic niche. Accumulation of Tregs and lymph node lymphangiogenesis was also COX-2/EP3-dependent. These results indicate that DCs induce a premetastatic niche via COX-2/EP3-dependent induction of SDF-1.
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