title: Colorectal cancer cell-derived extracellular vesicles induce phenotypic alteration of T cells into tumor-growth supporting cells with transforming growth factor-β1-mediated suppression.
abstract: Emerging studies on tumor cell-derived extracellular vesicles (EVs) have shown the biological significance in tumor development and microenvironment through reprogramming immune cells around cancer cells. In this study, we used colorectal cancer cells as EVs donor, and T cells as recipients to examine whether EVs impair the T cell function. As a result, we found that colorectal cancer cell-derived EVs (CRC-EVs) were enriched with TGF-β1. Interestingly, CRC-EVs induced phenotypic alteration of the T cells to Treg-like cells through activating TGF-β/Smad signaling and inactivating SAPK signaling. Furthermore, the CRC-EVs-induced-Treg-like cells had a remarkable tumor-growth promoting activity in vitro and in vivo. These results suggest that colorectal cancer cells utilize EVs to tame immune cells for their prosperity.
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Yamada
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kuranaga
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Kumazaki
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Shinohara
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008819:Mice, Nude; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D053773:Transforming Growth Factor beta1
keywords: TGF-β1; colorectal cancer; exosome; extracellular vesicle; tumor-stromal interaction