Inhibitory effect of an anti-prokineticin-1 antibody on liver metastases in mice

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09193
• 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: University of Fukui
• Principal Investigator: Goi Takanori 福井大学, 学術研究院医学系部門, 教授 (60225638)
• Co-Investigator(Kenkyū-buntansha): 山口 明夫 福井医療大学, 保健医療学部, 学長 (10174608)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Prokineticin1 / 抗体 / 肝転移

Outline of Final Research Achievements

The prokineticin family of angiogenic factors has the potential of becoming target molecules. Among them, prokineticin-1 (PROK1) is involved in the promotion of angiogenesis, tumor growth, and liver metastases in colorectal cancer. We manufactured our own anti-PROK1 antibody and verified its effect in inhibiting liver metastases and prolonging survival. The method involved creating liver metastasis model mice using human colorectal cancer cell lines. These mice were divided into anti-PROK1 antibody administration and control groups. Mice were treated intraperitoneally with antibodies or phosphate-buffered saline (control) every 3 days. The number of liver metastatic lesions and survival time of each group were compared. The number of metastatic lesions decreased and survival time was significantly prolonged in the antibody-treated group.
PROK1 antibody administration suppress liver metastasis suppression and prolonging the survival time of mice.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

大腸癌は肝転移、血行性転移をきたしやすく、その克服が生存率の向上の最大の鍵と考えられている。近年では標的分子の一つとして血管新生増殖因子が注目され、実際に血管新生増殖因子：VEGF(venous endothelial growth factor)因子に対する抗体Bevacizumabが化学療法との併用によって、切除不能大腸癌の生存率向上に貢献している。しかし大腸癌の撲滅という点については、さらなる治療法の開発が待ち望まれている。
PROK1遺伝子は、大腸癌細胞株を用いた実験系により、癌組織周囲の間質組織における血管新生の増殖から血行性転移への関わり認められ、新規治療への可能性が考えられる。