Development of a novel therapeutic approach based on the mechanism of tumor dissemination

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293286
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: Yonemitsu Yoshikazu 九州大学, 薬学研究科(研究院), 教授 (40315065)
• Co-Investigator(Kenkyū-buntansha): HARADA YUI 九州大学, 薬学研究院, 助教 (00608507) ; SAITO SATORU 九州大学, 薬学研究院, 学術研究員 (50634193)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 腹膜播種 / 悪性腫瘍 / 治療抵抗性

Outline of Final Research Achievements

Peritonitis carcinomatosa is an advanced and intractable state of gastrointestinal and ovarian cancer, where mechanistic elucidation might enable the development of more effective therapies. Peritoneal dissemination of this type of malignancy has been generally thought to initiate from "milky spots" of primitive lymphoid tissues in the peritoneal cavity. Spheroid formation strongly induced the expression of CXCR4 in an Sp1-dependent manner to promote niche-directed metastasis. Notably, disrupting sphere forma- tion or inhibiting Sp1 activity was sufficient to suppress tumor dissemination and potentiated chemosensitivity to 5-fluoro-uracil. Our findings illuminate mechanisms of peritoneal cancer dissemination and highlight the Sp1/CXCR4/CXCL12 signaling axis as a rational target for the development of therapeutics to manage this intractable form of malignancy.

Free Research Field

血管外科学、病理病態学、腫瘍免疫学