Activation of cancer-associated fibroblasts via the transfer of miR-125b containing extracellular vesicles from tumor cells

Research output: Conference Papers (RGC: 31A, 31B, 32, 33)Poster

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Author(s)

  • Victor Ma
  • Andrew Grimson
  • William C. Cho
  • Judy Lieberman

Detail(s)

Original languageEnglish
Publication statusPublished - Mar 2019

Conference

Title110th American Association for Cancer Research Annual Meeting (AACR2019)
LocationGeorgia World Congress Center
PlaceUnited States
CityAtlanta
Period29 March - 3 April 2019

Abstract

Tumor cells secrete elevated amounts of extracellular vesicles (EVs) as a mean of communication between them and other cells in the tumor microenvironment. Here, we established a series of breast cancer cell lines releasing fluorescent EVs to identify the common cell types that receive tumor EVs within the tumor microenvironment. Among the different cell types, cancer-associated fibroblasts consistently take up the most EVs from cancer cells. Using next generation sequencing, we find that miR-125b is among the top enriched miRNAs in EVs released by mouse isogenic triple-negative breast cancer 4T1 and 4TO7 cell lines. Co-injection of 4TO7 cells with 4T1 EVs results in an upregulation of fibroblast activation in vivo while blockage of miR-125b in 4T1 EVs rescues the effect indicating that EV-delivery of miR-125b is crucial for the fibroblast activation in mouse breast cancer models. Moreover, EVs from human breast cancer cells also contain abundant miR-125b and fibroblasts within the xenografted tumor that take up these EVs gain higher levels of miR-125b and upregulation of cancer-associated fibroblast markers. Both mouse and human fibroblasts that are transfected with miR-125b mimics show an activated phenotype similar to the knockdown of established miR-125b targets. In summary, normal fibroblasts within the tumor microenvironment actively take up the miR-125b-containing EVs from breast cancer cells and develop into cancer-associated fibroblasts.

Bibliographic Note

Full text of this publication does not contain sufficient affiliation information. With consent from the author(s) concerned, the Research Unit(s) information for this record is based on the existing academic department affiliation of the author(s).

Citation Format(s)

Activation of cancer-associated fibroblasts via the transfer of miR-125b containing extracellular vesicles from tumor cells. / Vu, Luyen Tien; Peng, Boya; Zhang, Daniel Xin; Ma, Victor; Grimson, Andrew; Cho, William C.; Lieberman, Judy; Le, Minh TN.

2019. Poster session presented at 110th American Association for Cancer Research Annual Meeting (AACR2019), Atlanta, United States.

Research output: Conference Papers (RGC: 31A, 31B, 32, 33)Poster