Anti-Metastatic Function of Extracellular Vesicles Derived from Nanog-Overexpressing Melanoma.

Tomohiro Hatakenaka,Nahoko Matsuki,Mikako Saito,Seiya Minagawa,Celine Swee May Khoo

doi:10.3390/curroncol29020088

Tomohiro Hatakenaka, Nahoko Matsuki + Show 3 more

Open Access

https://doi.org/10.3390/curroncol29020088

Copy DOI

Abstract

A metastatic melanoma cell line B16-F10 (F10) was modified to a more undifferentiated state by Nanog overexpression. The produced cell line Nanog+F10 showed a higher metastatic potential than F10. Instead of whole cells, the extracellular vesicles (EVs) therefrom were investigated about their possible role as an autovaccine against metastasis. EVs from Nanog+F10 cells (Nanog+F10-EVs) could suppress the metastasis, contrasting the EVs from less metastatic F10 cells (F10-EVs) enhanced metastasis. The involvement of TGF-β1 in the role of Nanog+F10-EVs was analyzed, as TGF-β1 was a secretory cytokine being affected most intensively by Nanog overexpression. It was suggested to be crucial that the TGF-β1 concentration in Nanog+F10-EVs should be as low as 1.6 pg/μg for its metastasis-suppressive role. In response to Nanog+F10-EVs, immunoreaction was observed in liver, indicating the specific decrease in the number of tumor-promotive CD163-positive macrophages. These indicate a possibility of Nanog+F10-EVs as a novel autovaccine candidate against melanoma metastasis.

Highlights

Extracellular vesicles (EVs) are nano-sized vesicles released by various cell types that have functions of cell-to-cell communication at various distances, maintenance of organ homeostasis, and induction of diseases [1,2,3]
The decrease in transforming growth factor (TGF)-β1 was observed in Nanog+F10 cells as compared to that in F10 cells
The decrease in TGF-β1 was observed in EVs derived therefrom

Summary

Introduction

Extracellular vesicles (EVs) are nano-sized vesicles released by various cell types that have functions of cell-to-cell communication at various distances, maintenance of organ homeostasis, and induction of diseases [1,2,3]. It is expected that the functions of EVs will reflect the properties of the original cells that released those EVs. A nutritive microenvironment or niche is required for disseminating tumor cells to engraft distant sites. Pancreatic ductal adenocarcinoma-derived EVs, for instance, may induce formation of a pre-metastatic niche in the liver [5]. Metastatic niche formation is not limited to distant sites. Prostate cancer-associated EVs modulate the tumor microenvironment to prepare a metastatic niche [6]. EVs containing ErbB2/CRK derived from bladder cancer can induce pre-metastatic niches in lung, liver, and bone [7]. Tumor cell-derived EVs are believed to stimulate tumorigenesis via promoting angiogenesis [8], remodeling of extracellular matrix [9], secretion of inflammatory molecules, and suppression of immune responses [10,11]

Methods

Results

Conclusion