Therapeutic targeting cancer-initiating cell markers by exosome miRNA

• Verfasst von: Kyuno, Daisuke [VerfasserIn]
• Verfasst von: Zhao, Kun [VerfasserIn]
• Verfasst von: Bauer, Nathalie [VerfasserIn]
• Verfasst von: Ryschich, Eduard [VerfasserIn]
• Verfasst von: Zöller, Margot [VerfasserIn]
• Titel: Therapeutic targeting cancer-initiating cell markers by exosome miRNA
• Titelzusatz: efficacy and functional consequences exemplified for claudin7 and EpCAM1
• Verf.angabe: Daisuke Kyuno, Kun Zhao, Nathalie Bauer, Eduard Ryschich and Margot Zöller
• Jahr: 2019
• Jahr des Originals: 2018
• Umfang: 9 S.
• Fussnoten: Available online 28 October 2018 ; Im Titel ist "1" in EpCAM1 hochgestellt ; Gesehen am 04.04.2019
• Titel Quelle: Enthalten in: Translational oncology
• Ort Quelle: Ann Arbor, Mich., 2008
• Jahr Quelle: 2019
• Band/Heft Quelle: 12(2019), 2, Seite 191-199
• ISSN Quelle: 1936-5233
• DOI: doi:10.1016/j.tranon.2018.08.021
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1662831900

Abstract

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.