2009 Fiscal Year Final Research Report

Chemokine Receptor Expression and Organ-Specific Metastasis in Esophageal Squamous Cell Carcinoma

Research Project

Project/Area Number	20790970
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Digestive surgery
Research Institution	Keio University
Principal Investigator	IRINO Tomoyuki Keio University, 医学部, 助教 (20445216)
Project Period (FY)	2008 – 2009
Keywords	癌
Research Abstract	We investigated the role of CCR7 in lymph node involvement in patients with esophageal squamous cell carcinoma (ESCC) with in vitro assays and in vivo metastasis model. First, we performed cell adhesion assay to assess the adhesive ability of CCR7-expressing cells, using native TE4 and TE4CCR7+, a CCR7-overexpressing cell line. Next, we examined how the CCR7-expressing cells behaved in vivo using newly-developed lymph node metastatic model mice. In a clinicopathological study, we analyzed 105 ESCC specimens with immunohistochemical staining. Cell adhesion assay revealed TE4CCR7+ had higher ability to attach to endothelial cells in the presence of the ligand (p<0.01). Furthermore, TE4CCR7+ cells showed earlier lymph node metastasis and proliferation in model mice. In the clinicopathological analysis, CCR7 expression was detected in 28 cases (27%), which was significantly associated with lymph node metastasis (p=0.04), 5-year RFS(p<0.01) and OS (p=0.02). These results strongly suggest that CCR7, in part, plays a critical role in lymph node metastasis and subsequent poor prognosis in patients with ESCC.