Elucidation of molecular mechanisms of chemotherapy resistance based on interactions between tumor cells and tumor microenvironment

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H05043
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Veterinary medical science
• Research Institution: The University of Tokyo
• Principal Investigator: Tomiyasu Hirotaka 東京大学, 大学院農学生命科学研究科(農学部), 助教 (70776111)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: エクソソーム / 化学療法耐性 / miRNA / 腫瘍微小環境 / 腫瘍免疫

Outline of Final Research Achievements

In this study, I focused on the interactions between tumor cells and immune cells via extracellular vesicles, exosomes, and investigated the molecular mechanisms involved in chemotherapy resistance in tumors.First, the molecular profiles of exosomes derived from canine lymphoma cells were comprehensively analyzed, and I identified the nucleic acids and proteins whose amounts within exosomes were different between chemotherapy agent-sensitive and resistant cells. In addition, it was suggested that CD82 protein has the functions to suppress the progression of tumors. Furthermore, it was revealed that tumor cell-derived exosomes significantly changed the expression levels of inflammatory cytokines in monocytes and lymphocytes and cell death was induced in cytotoxic T cells.
I believe that these results provided novel insights that contribute to the elucidation of the molecular pathology of neoplastic diseases.

Free Research Field

獣医学

Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍に対する化学療法において抗がん剤に対する耐性獲得は治療に限界をもたらす主たる要因となっているが、未だその分子機構の解明やその克服には至っていない。これまでの当該分野の研究では主に腫瘍細胞自身に起こる変化に着目してきたが、本研究では腫瘍細胞と周囲の微小環境、特に免疫細胞との相互作用という全く新たな着眼点からその分子病態を解析したものである。本研究から得られた成果は腫瘍性疾患の分子病態に関する新たな知見を提供するものであり、獣医学領域のみならず人医学領域における研究にも貢献するものと考えている。