Clinical significance of glycosylceramide in the immune microenvironment of breast cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17578
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Niigata University
• Principal Investigator: Moro Kazuki 新潟大学, 医歯学総合病院, 助教 (10745566)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 乳癌 / グルコシルセラミド / セラミド / スフィンゴシン１リン酸 / リピドミクス解析 / RNAシークエンス / マクロファージ

Outline of Final Research Achievements

Ceramide and sphingosine-1-phosphate (S1P) are important regulatory molecules that maintain a dynamic balance called the sphingolipid rheostat and play opposing roles in cell survival and death. Glucosylceramide is known to have anticancer activity. The purpose of this study was to reveal the anticancer activity of glucosylceramide, identifying a potential new therapeutic agent in breast cancer.
Results: The tumor size of mice treated with glucosylceramide was significantly smaller than that of mice in the control group. The ceramide-to-S1P concentration ratio in tumors was significantly higher in mice treated with glucosylceramide than in control-treated mice.
Conclusions: Breast tumors could enhance their survival by increasing S1P conversion from ceramide, whereas oral administration of glucosylceramide suppressed tumor growth by increasing ceramide conversion from S1P. Oral administration of glucosylceramide is a promising basis for a new therapeutic approach.

Free Research Field

乳癌

Academic Significance and Societal Importance of the Research Achievements

乳癌治療の進歩にもかかわらず乳癌死亡数は年々増加し続けており、腫瘍免疫の重要性が高まっている。腫瘍免疫微小環境の調節因子として脂質でありながらタンパク質と同じように情報伝達物質として作用する「脂質メディエーター分子」が注目されている。本研究ではグルコシルセラミド経口投与により、腫瘍組織内における脂質メディエーターのバランスを変化させ、腫瘍増殖を抑制することが示された。本研究によりグルコシルセラミド経口投与には腫瘍増殖を抑制させる効果を有する可能性があることが示された。