Analysis of novel pathogenesis of cancer-associated fibroblast involved in age-related stromal exosome changes

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06841
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Tokyo Medical University
• Principal Investigator: Umezu Tomohiro 東京医科大学, 医学部, 講師(特任) (40385547)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: miRNA / 細胞外小胞 / 骨髄間質細胞 / がん微小環境 / aging

Outline of Final Research Achievements

Bone marrow stromal cells (BMSCs) and their exosomes are a promising area of cancer therapy; however, little is known about the age of BMSCs from which the exosomes came. Here, we investigated therapeutic effects of BMSC exosomes derived from young and elderly donors.
The exosomes were isolated from conditioned medium of BMSCs. We performed exosomal miRNA profiling, and found that the donor’s age decides senescent changes in BMSC, and exosomes derived from young BMSCs could block MM cell-induced angiogenesis in Matrigel plug. We also noted young BMSC-specific exosomal miRNA, such as miR-340. Of note is that the anti-angiogenic effect was potentiated by modifying exosomes of elderly BMSCs; exosomes are directly transfected with miR-340. Our results suggest that the BMSC exosomes is able to transfer the miRNAs, which have the ability to inhibit angiogenesis. The present study provides a new insight toward exosome-based cancer therapy by reconstruction of BMSC-derived exosomes.

Free Research Field

分子腫瘍学