Construction of scientific foundation for drug delivery technology using caveolae vesicles

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22565
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Kumamoto University
• Principal Investigator: YAMAGUCHI Tomoya 熊本大学, 大学院先導機構, 准教授 (70452191)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: カベオラ / 人工小胞 / ドラッグデリバリー / 薬剤伝達法 / がん治療

Outline of Final Research Achievements

Caveolae are 50-100 nm invaginations of the plasma membrane that play various physiological roles. Caveolin-1 (CAV1) is an essential structural component of caveolae, and cavin-1 (also known as PTRF), a soluble cytosolic protein, associates with CAV1 and prevents its lysosomal degradation. This association enables CAV1 and cavin-1 to be stably confined to the plasma membrane, a process that is thought to be an indispensable prerequisite for caveolae formation.
We previously have reported that the receptor tyrosine kinase-like orphan receptor 1 (ROR1) sustains prosurvival signaling directly downstream of the lineage-survival oncogene NKX2-1/TTF-1 in lung adenocarcinoma. Here we report an unanticipated function of this receptor tyrosine kinase (RTK) as a scaffold of cavin-1 and caveolin-1 (CAV1), two essential structural components of caveolae. This kinase-independent function of ROR1 facilitates the interactions of cavin-1 and CAV1 at the plasma membrane.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

人工的に精製したカベオラから生まれる小胞は、従来の合成ミセル等に代表される試験管内での再構築系に比べ、安く大量に作ることができることから、精製したカプセル剤を医学的に応用できると考える。本研究により科学的な研究成果の基盤情報に基づいて、今回研究代表者らが提案したROR1分子によるカベオラを介した機能的人工小胞の作製は、薬剤を腫瘍など体内の必要な場所に正確に届けるDDSとしての可能性を大いに有しており、標的細胞としての癌へのこれまでにない薬剤の送達手段方法の確立につながる可能性を有しており、新しい治療法につながると期待される。