Novel strategies to target the premetastatic niche for cancer metastasis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10568
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nagoya University
• Principal Investigator: MIZUNO TAKASHI 名古屋大学, 医学部附属病院, 病院講師 (90444413)
• Co-Investigator(Kenkyū-buntansha): 梛野 正人 名古屋大学, 医学系研究科, 教授 (20237564) ; 横山 幸浩 名古屋大学, 医学系研究科, 寄附講座教授 (80378091) ; 國料 俊男 名古屋大学, 医学部附属病院, 講師 (60378023) ; 山口 淳平 名古屋大学, 医学部附属病院, 助教 (00566987)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Pre-metastatic niche / TPX2

Outline of Final Research Achievements

TPX2 was highly expressed in pancreatic cancer cell lines (PANC1 and KLM1) and colon cancer cell lines (DLD1 and HCT15). A TPX2 siRNA induced the TPX2 suppression and MCP1 overexpression in PANC1 and KLM1 cells. The culture medium of TPX2 siRNA-transfected pancreatic cancer cells showed an inhibitory effect on the proliferation and invasion of cancer cells. Factors secreted by TPX2 siRNA-transfected pancreatic cancer cells may cause a secondary effect on pancreatic cancer.
Pre-exposure to 5-FU significantly enhanced its anticancer effect on the proliferation of KLM1, KP4 and DLD1 cells. However, there were no significant differences in the motility and invasion between cells that were and were not pre-exposed to 5-FU. The secondary effect was not simple and uniform in terms of cancer cell damage. Further investigations will be required for clinical applications. However, our data indicate the potential for a new therapy using TPX2 siRNA to improve the cancer prognosis.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、TPX2抑制および抗癌剤5FUによる細胞傷害後の培養液に副次的効果があり、その効果が単純かつ画一的なものではないことを明らかにした。また、新たな知見が明らかになっただけでなく、新規治療法の可能性も示唆しており、本研究成果の学術的、社会的意義は大きい。