Oncotarget

Research Papers:

Cancer-associated fibroblasts enhance metastatic potential of lung cancer cells through IL-6/STAT3 signaling pathway

Limin Wang, Limin Cao, Huimin Wang, Boning Liu, Qicheng Zhang, Zhaowei Meng, Xiang Wu, Qinghua Zhou and Ke Xu _

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Oncotarget. 2017; 8:76116-76128. https://doi.org/10.18632/oncotarget.18814

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Abstract

Limin Wang1,*, Limin Cao1,*, Huimin Wang1,*, Boning Liu1, Qicheng Zhang1, Zhaowei Meng2, Xiang Wu3, Qinghua Zhou1 and Ke Xu1

1Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China

2Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China

3Core Facility Center, Tianjin Medical University General Hospital, Tianjin 300052, China

*These authors have contributed equally to this work

Correspondence to:

Ke Xu, email: [email protected]

Keywords: lung cancer, cancer-associated fibroblasts, metastasis, EMT, IL-6

Received: December 08, 2016     Accepted: June 02, 2017     Published: June 28, 2017

ABSTRACT

Recent studies indicate that cancer-associated fibroblasts (CAFs) are involved in tumor growth, invasion and metastasis, however, the underling mechanisms remain unclear. In the present study, we investigated the role of CAFs on the metastatic potential of lung cancer cells. The stromal fibroblasts we isolated from lung cancer tissues presented CAFs characteristics with high levels of α-smooth muscle actin (α-SMA) and fibroblast-activating protein (FAP). Our data showed that the conditioned medium from cultured CAFs (CAF-CM) dramatically enhanced migration and invasion of lung cancer cells. CAF-CM induced epithelial-mesenchymal transition (EMT) by regulating the expression of EMT-associated markers E-cadherin and vimentin, and also modulated metastasis-related genes MMP-2 and VEGF both in vitro and in vivo. Further mechanistic studies demonstrated that CAFs enhanced the metastatic potential of lung cancer cells by secreting IL-6, subsequently activating of JAK2/STAT3 signaling pathway. Additionally, the inhibition of IL-6/STAT3 signaling pathway by IL-6 neutralizing antibody or specific inhibitors of JAK2/STAT3 reversed CAF-CM induced EMT and migration of lung cancer cells. Taken together, these findings revealed a novel mechanism that CAFs induced EMT and promoted metastasis of lung cancer cells through the IL-6/STAT3 signaling pathway.


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