Gallbladder Cancer Cell-Derived Exosome-Mediated Transfer of Leptin Promotes Cell Invasion and Migration by Modulating STAT3-Mediated M2 Macrophage Polarization.

Songling Zhao,Yunxia Liu,Yuehua Li,Hao Zou,Ke Lin,Qiang Kang,Lixin Liu,Linhai He,Ulises Urzua

doi:10.1155/2022/9994906

Songling Zhao, Yunxia Liu + Show 7 more

Open Access

https://doi.org/10.1155/2022/9994906

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Abstract

Tumor-associated macrophage (TAM) is a major component of tumor microenvironment (TME) and plays critical role in the progression of cancer metastasis. However, TAM-mediated regulation in gallbladder cancer (GBC) has not been fully characterized. Here, we found that exosomes derived from GBC cell polarized macrophage to M2 phenotype, which then facilitated the invasion and migration of GBC cells. We discovered that leptin was enriched in GBC cell-derived exosomes. Exosomal leptin levels promoted invasion and migration of GBC-SD cells. The inhibition of leptin not only attenuated M2 macrophage of polarization but also inhibited the invasive and migratory ability of GBC cell. In addition, GBC-SD cell-derived exosomal leptin induced M2 polarization of macrophage via activation of STAT3 signal pathway. Taken together, our results suggested that GBC cells secrete exosome-enclosed leptin facilitated cell invasion and migration via polarizing TAM.

Highlights

Gallbladder cancer (GBC) is the most common biliary tract malignancy
We examined the effect of GBC-SD cell-derived exosomes on macrophage polarization
Our data showed that exosomes derived from GBC cells promote the polarization of macrophage to M2-subtype

Summary

Introduction

Gallbladder cancer (GBC) is the most common biliary tract malignancy. It is important to understand the underlying mechanism of gallbladder cancer and progression. Tumor-associated macrophage (TAM), which is a major component of tumor microenvironment (TME), plays critical role in the crosstalk between cancer cells and TME. TAM is defined more closely resemble M2-polarized macrophage [1]. Emerging evidence indicated that M2 macrophage is able to enhance cancer progression [2] and metastasis [3]. The presence of M2 macrophages is supposed to be correlated with a poor prognosis for breast cancer [4], colorectal cancer [5], and hepatocellular cancer [6]. The role of M2-subtype macrophage in the development of GBC has not been fully characterized

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