Bronchoalveolar Lavage Fluid-Derived Exosomes: A Novel Role Contributing to Lung Cancer Growth.

Yibao Yang,Jenni Firrman,Weidong Xiao,Junlu Wu,Zujun Sun,Chenzheng Gu,Xuan Wang,Ping Ji,Junjun Sun,Dong Li,Wenqing Quan,Hao Zhou,Anquan Shang

doi:10.3389/fonc.2019.00197

Abstract

Exosomes are nanovesicles produced by a number of different cell types and regarded as important mediators of cell-to-cell communication. Although bronchoalveolar lavage fluid (BALF) has been shown to be involved in the development of tumors, its role in lung cancer (LC) remains unclear. In this article, we systemically studied BALF-derived exosomes in LC. C57BL/6 mice were injected with Lewis lung carcinoma cells and exposed to non-typeable Haemophilus influenza (NTHi) lysate. The analysis showed that the growth of lung tumors in these mice was significantly enhanced compared with the control cohort (only exposure to air). Characterization of the exosomes derived from mouse BALF demonstrated elevated levels of tumor necrosis factor alpha and interleukin-6 in mice exposed to NTHi lysates. Furthermore, abnormal BALF-derived exosomes facilitated the development of LC in vitro and in vivo. The internalization of the BALF-derived exosomes contributed to the development of LC tumors. Collectively, our data demonstrated that exosomes in BALF are a key factor involved in the growth and progression of lung cancer.

Highlights

Lung cancer (LC) is a serious public health problem and a major cause of cancer-related death worldwide
The Abbreviations: LC, lung cancer; IL-6, interleukin-6; tumor necrosis factor-α (TNF-α), tumor necrosis factor alpha; TME, tumor microenvironment; EMT, epithelial-mesenchymal transition; Chronic obstructive pulmonary disease (COPD), chronic obstructive pulmonary disease; BALF, bronchoalveolar lavage fluid; LLC, Lewis lung carcinoma; NTHi, non-typeable Haemophilus influenza; air-Exos, exosomes from mice exposed to air; NTHi-Exos, exosomes from mice exposed to NTHi lysates
After 3 weeks, we found that the mice exposed to NTHi lysates exhibited a significant increase in lung tumor growth compared with those exposed to air

Summary

Introduction

Lung cancer (LC) is a serious public health problem and a major cause of cancer-related death worldwide. Pulmonary adenocarcinoma is the major histological type of lung tumors [2]. Emerging evidence indicates that the tumor microenvironment (TME) is closely associated with tumor progression [3]. Studies investigating the communication between the TME and tumor cells have mostly been limited to soluble factors produced by inflammatory cells in the TME, which may contribute to the development of cancer [4, 5]. A growing body of evidence suggests that exosomes mediate cell-to-cell communication [6, 7], and play an important role in tumor progression and metastasis [8,9,10]

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Results

Conclusion