Tumor-derived Exosomal MiR-1247-3p Induces Cancer-associated Fibroblast Activation to Foster Lung Metastasis of Liver Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jan 17

PMID 29335551

Citations 494

Authors

Tian Fang

HongWei Lv

GuiShuai Lv

Ting Li

Changzheng Wang

Qin Han

Lexing Yu

Bo Su

Linna Guo

Shanna Huang

Dan Cao

Liang Tang

Shanhua Tang

Mengchao Wu

Wen Yang

Hongyang Wang

Affiliations

Soon will be listed here.

Abstract

The communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high-metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin-NF-κB signaling in fibroblasts. Activated CAFs further promote cancer progression by secreting pro-inflammatory cytokines, including IL-6 and IL-8. Clinical data show high serum exosomal miR-1247-3p levels correlate with lung metastasis in HCC patients. These results demonstrate intercellular crosstalk between tumor cells and fibroblasts is mediated by tumor-derived exosomes that control lung metastasis of HCC, providing potential targets for prevention and treatment of cancer metastasis.

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