Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer

被引：1011

作者：

Fang, Tian ^{[1
]}

Lv, Hongwei ^{[1
]}

Lv, Guishuai ^{[1
,2
]}

Li, Ting ^{[1
]}

Wang, Changzheng ^{[1
]}

Han, Qin ^{[1
]}

Yu, Lexing ^{[1
,2
]}

Su, Bo ^{[3
]}

Guo, Linna ^{[1
,2
]}

Huang, Shanna ^{[1
,2
]}

Cao, Dan ^{[1
,2
]}

Tang, Liang ^{[1
,2
]}

Tang, Shanhua ^{[1
,2
]}

Wu, Mengchao ^{[1
,2
]}

Yang, Wen ^{[1
,2
]}

Wang, Hongyang ^{[1
,2
,4
]}

机构：

[1] Second Mil Med Univ, Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, Shanghai 200438, Peoples R China

[2] Natl Ctr Liver Canc, Shanghai 201805, Peoples R China

[3] Tongji Univ, Shanghai Pulm Hosp, Sch Med, Cent Lab, Shanghai 200433, Peoples R China

[4] Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes, Shanghai 200032, Peoples R China

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

STROMAL FIBROBLASTS; GROWTH; MICROENVIRONMENT; MYOFIBROBLAST; COMMUNICATION; BIOGENESIS; PROGNOSIS; CARCINOMA; INVASION; MIRNA;

D O I：

10.1038/s41467-017-02583-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 beta 1-integrin-NF-kappa B 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.

引用

页数：13

共 48 条

[1]

CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth [J].