Visualization of exosome-mediated miR-210 transfer from hypoxic tumor cells

Kyung Oh Jung; Hyewon Youn; Chul-Hee Lee; Keon Wook Kang; June-Key Chung

doi:10.18632/oncotarget.14247

Visualization of exosome-mediated miR-210 transfer from hypoxic tumor cells

Oncotarget. 2017 Feb 7;8(6):9899-9910. doi: 10.18632/oncotarget.14247.

Authors

Kyung Oh Jung^{1

2

3

4}, Hyewon Youn^{1

3

5}, Chul-Hee Lee^{1

2

3}, Keon Wook Kang^{1

3}, June-Key Chung^{1

2

3}

Affiliations

¹ Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea, 110-799.
² Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea, 110-799.
³ Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea, 110-799.
⁴ Current affiliation: Department of Radiation Oncology & Medical Physics, Stanford University, CA, USA, 94305.
⁵ Cancer Imaging Center, Seoul National University Hospital, Seoul, Korea, 110-799.

Abstract

Cancer cells actively release exosomes carrying specific cellular components, such as proteins, mRNA, and miRNA, to communicate with various cells in the tumor microenvironment. We visualized exosome-mediated transfer of miR-210 from hypoxic breast cancer cells to neighboring cells using a miR-210 specific reporter system. By in vitro and in vivo visualization, we found that exosomes with miR-210 were transferred to cells in the tumor microenvironment and that miR-210 was involved in expression of vascular remodeling related genes, such as Ephrin A3 and PTP1B, to promote angiogenesis. These results indicate that cellular components, such as miRNAs from hypoxic cancer cells, spread to adjacent cancer cells in the tumor microenvironment via exosomes and influence tumor progression.

Keywords: breast cancer; exosome; hypoxia; miR-210; tumor microenvironment.

MeSH terms

3T3 Cells
Animals
Biological Transport
Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Line, Tumor
Deferoxamine / pharmacology
Ephrin-A3 / genetics
Ephrin-A3 / metabolism
Exosomes / metabolism*
Exosomes / pathology
Female
Gene Expression Regulation, Neoplastic
Genes, Reporter
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Luciferases / genetics
Luciferases / metabolism
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics
MicroRNAs / metabolism*
Microscopy, Confocal*
Neovascularization, Pathologic
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
RAW 264.7 Cells
Red Fluorescent Protein
Transfection
Tumor Hypoxia*
Tumor Microenvironment*

Substances

Ephrin-A3
Luminescent Proteins
MIRN210 microRNA, mouse
MicroRNAs
Green Fluorescent Proteins
Luciferases
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Ptpn1 protein, mouse
Deferoxamine