The mechanism of promoting liver metastasis caused by CXCL 12 and fundamental research for innovative therapeutic development in intrahepatic cholangiocarcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08709
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: MASUDA Tosirou 熊本大学, 病院, 非常勤診療医師 (50551256)
• Co-Investigator(Kenkyū-buntansha): 山下 洋市 熊本大学, 大学院生命科学研究部(医), 准教授 (00404070) ; 岡部 弘尚 熊本大学, 病院, 非常勤診療医師 (40573621) ; 今井 克憲 熊本大学, 大学院生命科学研究部(医), 助教 (60555746) ; 中川 茂樹 熊本大学, 病院, 非常勤診療医師 (10594872) ; 日比 泰造 熊本大学, 大学院生命科学研究部(医), 教授 (10338072)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肝内胆管癌 / CXCL12 / 転移 / cDNAマイクロアレイ / 免疫化学組織染色

Outline of Final Research Achievements

Intrahepatic cholangiocarcinoma (ICC) accounts for about 5-10% of primary liver cancers in Japan and is one of the poorest prognostic cancers with a high rate of recurrence after curative hepatic resection. The aim of this study was to elucidate the mechanism of metastasis and recurrence in ICC and to identify novel therapeutic targets. We evaluated resected specimens of primary and metastatic ICCs by cDNA microarray and immunohistochemical staining, and showed that CXCL12, which is one of chemokines, was significantly upregulated in liver metastases compared to primary tumors, and that the prognosis after liver resection was significantly worse in patients with high CXCL12 expression. In addition, we also showed that CXCL12 suppression in human cholangiocarcinoma cell lines suppressed their invasive and migratory potential, indicating that CXCL12 may be a potential therapeutic target in ICC.

Free Research Field

消化器外科、肝癌

Academic Significance and Societal Importance of the Research Achievements

肝内胆管癌 (ICC)は肝癌の約5－10%を占めており、肝切除後も高率に再発をきたす予後不良な癌の一つです。　我々は、ケモカインCXCL12が転移巣の切除標本で有意に高発現すること、肝切除後の予後に関与していること、ヒト胆管癌細胞株におけるCXCL12抑制による浸潤能及び遊走能が抑制効果を示し、CXCL12がICCにおける治療ターゲットになりうる可能性を示しました。