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

About this project

Project/Area Number
Research Category
Grant-in-Aid for Scientific Research (C)
Allocation Type
  • Multi-year Fund
Review Section / Research Field
  • Biological Sciences > Biological Sciences > Oncology > Tumor biology
Research Institution
  • Tokyo Medical University
Project Period (FY)
2015-04-01 〜 2018-03-31
Project Status
Budget Amount*help
4,810,000 Yen (Direct Cost: 3,700,000 Yen Indirect Cost: 1,110,000 Yen)
Funding Program
Grants-in-Aid for Scientific Research

Research Abstract

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.

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