The role of Prostanoid in premetastatic niche in regional lymph nodes.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Kitasato University
• Principal Investigator: Amano Hideki 北里大学, 医学部, 講師 (60296481)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: プロスタグランジンE2 / 縦隔リンパ節転移 / pre-metastatic niche / EP3 / SDF-1

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.

Free Research Field

呼吸器外科、薬理学