Basic study on apoptosis-inducing therapy by activation of TRAIL pathway in canine hemangiosarcoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08101
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Gifu University
• Principal Investigator: Sakai Hiroki 岐阜大学, 応用生物科学部, 教授 (40283288)
• Co-Investigator(Kenkyū-buntansha): 村上 麻美 岐阜大学, 応用生物科学部, 助教 (30597125)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 犬 / TRAIL / 腫瘍 / 血管肉腫 / 乳腺腫瘍

Outline of Final Research Achievements

Hemangiosarcoma (HSA) occurs frequently in dogs. As in humans, the canine HSA is highly malignant with a very poor prognosis despite treatment with surgery and chemotherapy for early metastasis and dissemination. However, no effective treatment strategy has been developed. Another tumor that can serve as a human model is the canine mammary tumor (CMT). CMT is the most common tumor in female dogs. In addition to research as a model animal for human breast cancers, study for development of new therapies for CMT is needed because of its veterinary clinical importance. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is one of the most prominent anti-tumor cytokines. I aimed to verify the effects of TRAIL on HSA and CMT. izTRAIL induced apoptosis in canine HSA cell lines. Furthermore, a similar apoptosis-inducing action was observed in cell lines derived from CMT, suggesting the broad applicability of TRAIL in veterinary medicine.

Free Research Field

獣医病理学

Academic Significance and Societal Importance of the Research Achievements

有効な治療法がない悪性度の高い犬の血管肉腫と，臨床の現場でよく遭遇する犬の乳腺腫瘍の抗腫瘍サイトカインTRAILを用いた新規治療法の開発にあたり，間葉系由来腫瘍および上皮系腫瘍ともに抗腫瘍効果が見られ，獣医領域での腫瘍の治療におけるTRAILの広い適用の可能性を示した。また，血管肉腫に対するTRAILの抗腫瘍効果は，ヒトの血管肉腫も含め，世界で初めて明らかにされたことであり，医学領域で，その発生が非常にまれで，研究が困難な腫瘍の一つである血管肉腫に対して，研究・新規治療法の開発のモデルとして犬の血管肉腫を用いうる可能性を示すことができた。