Elucidation of molecular mechanisms of a lipid mediator in resistance of breast cancer hormone therapy and its clinical significance

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10538
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Niigata University
• Principal Investigator: Ikarashi Mayuko 新潟大学, 医歯学総合病院, 医員 (50790284)
• Co-Investigator(Kenkyū-buntansha): 永橋 昌幸 新潟大学, 医歯学総合病院, 研究准教授 (30743918) ; 土田 純子 新潟大学, 医歯学総合病院, 専任助教 (90769415) ; 小山 諭 新潟大学, 医歯学系, 教授 (10323966)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 脂質メディエーター / スフィンゴシン－1－リン酸 / 乳癌 / ホルモン療法

Outline of Final Research Achievements

Elucidation and overcoming of resistance mechanism in breast cancer hormone therapy is an important clinical issue. Sphingosine-1-phosphate (S1P) is a lipid mediator that acts as a cell signal transmitter in the same way as a protein, although it is a lipid. The aim of this study was to elucidate the resistance mechanism of hormone therapy through S1P and to establish the research basis for the development of new treatments. In this study, we found that FTY720, which blocks the S1P signaling pathway, suppress the proliferation of hormone therapy-resistant breast cancer cells. In addition, we performed a lipidomics analysis using clinical samples and compared the association with clinicopathologic factors. As a result, we found that high plasma S1P levels are significantly associated with lymph node metastasis in breast cancer patients.

Free Research Field

腫瘍外科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果の学術的意義として、（１）脂質メディエータであるS1Pがホルモン療法耐性機序に関与しており、S1Pシグナルを標的とした治療の有効性が実験レベルで明らかになったことと、（２）臨床検体において、S1Pのリンパ節転移との関連が示され、ホルモン陽性乳癌におけるS1Pの重要性が示唆されてことが挙げられる。本研究の成果により、新しいホルモン療法耐性機序に基づいた標的治療薬の開発へつながることが期待される。