Therapeutic targeting cancer-initiating cell markers by exosome miRNA: efficacy and functional consequences exemplified for claudin7 and EpCAM1
AIM: Transfer of exosomes (Exo) miRNA was described interfering with tumor progression. We here explored for claudin7 (cld7) and EpCAM (EpC), cancer-initiating-cell markers in colorectal and pancreatic cancer, the efficacy of Exo loading with miRNA and miRNA transfer. METHODS: Exo were collected fro...
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| Main Authors: | , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
2019
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| In: |
Translational oncology
Year: 2018, Volume: 12, Issue: 2, Pages: 191-199 |
| ISSN: | 1936-5233 |
| DOI: | 10.1016/j.tranon.2018.08.021 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.tranon.2018.08.021 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1936523318302791 
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| Author Notes: | Daisuke Kyuno, Kun Zhao, Nathalie Bauer, Eduard Ryschich and Margot Zöller |
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| 245 | 1 | 0 | |a Therapeutic targeting cancer-initiating cell markers by exosome miRNA |b efficacy and functional consequences exemplified for claudin7 and EpCAM1 |c Daisuke Kyuno, Kun Zhao, Nathalie Bauer, Eduard Ryschich and Margot Zöller |
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| 520 | |a AIM: Transfer of exosomes (Exo) miRNA was described interfering with tumor progression. We here explored for claudin7 (cld7) and EpCAM (EpC), cancer-initiating-cell markers in colorectal and pancreatic cancer, the efficacy of Exo loading with miRNA and miRNA transfer. METHODS: Exo were collected from nontransformed mouse (NIH3T3) and rat lung fibroblasts (rFb), which were transfected with Tspan8 cDNA (NIH3T3-Tspan8, rFb-Tspan8). Exo were loaded by electroporation with miRNA. The transfer of Exo-miRNA was evaluated in vitro and in vivo in a rat pancreatic (ASML) and a human colon (SW948) cancer line. RESULTS: NIH3T3-Tspan8- or rFb-Tspan8-Exo were efficiently loaded with cld7- or EpC-miRNA. Exo targeting in vivo was strongly improved by tailoring with Tspan8. Exo-miRNA transfer into tumor targets promoted cld7, respectively, EpC downregulation by 33%-60%. Cld7 silencing was accompanied by reduced expression of additional cancer-initiating cell markers and NOTCH. EpC silencing reduced vimentin, N-cadherin, and Nanog expression. The Exo-miRNA transfer affected anchorage-independent growth, motility, and invasion. CONCLUSIONS: Exo are efficiently loaded with miRNA, miRNA-delivery being supported by Exo tailoring. Partial cld7 and EpC silencing by Exo miRNA affects metastasis-promoting tumor cell activities. The findings suggest miRNA loading of tailored Exo as an easy approachable and efficient adjuvant therapy. | ||
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