Elucidation of the role of CD44 variant molecule in radiation resistance ability in canine cancer stem cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Azabu University
• Principal Investigator: Sahara Hiroeki 麻布大学, 獣医学部, 教授 (10260762)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: CD44 / 癌 / 放射線治療 / xCT / イヌ

Outline of Final Research Achievements

In this study, CD44 variant form, CD44v, was expressed in canine tumor tissues, and functional analysis by using canine breast cancer cells showed that CD44v was induces synthesis of the endogenous antioxidant glutathione and increased radiation resistance. Furthermore, when the gene expression of canine cystine transporter (xCT) was compared between breast cancer tissue and surrounding normal tissue, it was significantly upregulated in tumor tissue, and xCT was found to be resistant to oxidative stress from experiments with xCT inhibitors using canine breast cancer cells. These results suggest that CD44v and xCT have important effects on radiotherapy resistance relating in oxidative stress in canine tumors.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究では実際のイヌの腫瘍症例において、CD44バリアントフォームが存在し、それと相互作用して酸化ストレス耐性を獲得するとされるxCT分子の腫瘍組織での発現を見いだしたのは、本研究が初めてある。その成果は国際学術雑誌であるVet. Med. Sci., 2021, 7: 577~585.にも掲載された。そして本知見は放射線治療の抵抗性に関するものと関連し、獣医癌治療の改善にも寄与することが考えられる。