| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
Lung cancer has remained one of the most deadliest cancers worldwide accounting for 18% of all cancer deaths. We investigated the contribution of COX-2/PGE2 in the formation of a premetastatic niche and LNM. A murine model of LLC cell metastasis revealed that COX-2 is expressed in DCs from the early stage in the lymph node, and COX-2 inhibition suppressed mediastinal LNM. SDF-1 was elevated in DCs before LLC cell infiltration to the lymph nodes, and a COX-2 inhibitor, a SDF-1 antagonist, and a CXCR4 antibody reduced LNM. Moreover, LNM was reduced in EP3 knock out mice and stimulation of cultured DCs with an EP3 agonist increased SDF-1 production. The injection of EP3-KO CD11c+DCs reduced accumulation of SDF-1+CD11c+DCs in regional LNs and LNM in LLC-injected mice. Accumulation of Tregs and lymph node lymphangiogenesis, was also COX-2/EP3-dependent. These results indicate that DCs induce a premetastatic niche during LNM via COX-2/EP3-dependent induction of SDF-1.
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