Colorectal cancer cell-derived extracellular vesicles induce phenotypic alteration of T cells into tumor-growth supporting cells with transforming growth factor-β1-mediated suppression

Nami Yamada; Yuki Kuranaga; Minami Kumazaki; Haruka Shinohara; Kohei Taniguchi; Yukihiro Akao

doi:10.18632/oncotarget.7041

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Research Papers:

Colorectal cancer cell-derived extracellular vesicles induce phenotypic alteration of T cells into tumor-growth supporting cells with transforming growth factor-β1-mediated suppression

Nami Yamada _, Yuki Kuranaga, Minami Kumazaki, Haruka Shinohara, Kohei Taniguchi and Yukihiro Akao

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Oncotarget. 2016; 7:27033-27043. https://doi.org/10.18632/oncotarget.7041

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Abstract

Nami Yamada1, Yuki Kuranaga1, Minami Kumazaki1, Haruka Shinohara1, Kohei Taniguchi1 and Yukihiro Akao1

1 United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan

Correspondence to:

Nami Yamada, email:

Keywords: colorectal cancer, exosome, extracellular vesicle, TGF-β1, tumor-stromal interaction

Received: August 20, 2015 Accepted: January 20, 2016 Published: January 27, 2016

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.

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Research Papers:

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