Development of a cancer metastasis suppressor decoy peptide based on PLOD2-Integrin hydroxylation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09626
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Niigata University of Health and Welfare (2022-2023); Niigata University (2021)
• Principal Investigator: Saito Ken 新潟医療福祉大学, 医療技術学部, 教授 (70426584)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん浸潤転移 / 水酸化酵素 / ペプチド

Outline of Final Research Achievements

As a new tool for the treatment of oral and head and neck cancer, the development of peptide drugs that effectively suppress cancer invasion and metastasis while maintaining oral and head and neck function was investigated.
The peptide development was based on the previously reported interaction between the lysine hydroxylase PLOD2 and integrin beta-1. The resulting beta-1 peptide was found to inhibit oral cancer cell migration and the PLOD2-integrin beta-1 pathway.
In addition, in combination with the cisplatin, cisplatin sensitivity was significantly increased. On the other hand, the development of peptides (CPPs) to deliver beta-1 peptides to target cells has been difficult and remains a challenge for the future.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究から得られたbeta-1ペプチドは、PLOD2高発現の悪性腫瘍の浸潤・転移抑制と薬剤感受性を惹起することが考えられます。従って、本ペプチドの効果は、口腔・頭頸部癌だけでなく骨肉腫(PLOD2高発現）へ応用可能であり、現在、骨肉腫でのbeta-1ペプチドの作用を詳細に検討しています。また、ペプチドはデザイン改変の自由度が高く、抵抗原生、良好な吸収と代謝性そして生体低侵襲性である利点を持つことから優れた創薬開発ツールとなり得えます。即ち、本研究ペプチドの研究開発は、難治性の癌の浸潤・転移制御によるがん病巣の拡大を封じるものとなり、今後、標的細胞へ特異的にデリバリーする方法も検討していきます。