Chloroquine Inhibits Stemness of Esophageal Squamous Cell Carcinoma Cells Through Targeting CXCR4-STAT3 Pathway.

Dongli Yue,Lidong Wang,Yu Ping,Anqi Li,Yi Zhang,Shasha Liu,Yamin Qiao,Dong Wang,Renyin Chen,Xinfeng Chen,Feng Wang,Guohui Qin,Xiaojuan Shi,Daiqun Zhang,Song Zhao

doi:10.3389/fonc.2020.00311

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers worldwide. Recent studies have shown that cancer stem cells (CSCs) are present in ESCC, are thought to lead to aggressive tumor behavior and the prognosis. The CXC chemokine receptor 4 (CXCR4), is regarded as a putative CSCs marker in various malignancies. Here, we demonstrate that CXCR4 played a key role in ESCC progression and CXCR4 positive ESCC cells possessed stem-like properties. Furthermore, the anti-malarial agent chloroquine (CQ) targeted CXCR4-positive ESCC cells via STAT3 pathway. Therefore, CQ with anti-CSCs effects may be an effective adjunct to current ESCC chemotherapy regimens.

Highlights

Esophageal cancer is the fifth and eighth most frequent cause of cancer-related death in male and female worldwide, respectively [1]
We found CXC chemokine receptor 4 (CXCR4) was significantly up-regulated in Esophageal squamous cell carcinoma (ESCC) specimens, compared with non-cancerous specimens (Figure 1A)
We found that CXCR4 protein expression was significantly upregulated in ESCC compared with the adjacent non-cancerous tissues (Figure 2A)

Summary

Introduction

Esophageal cancer is the fifth and eighth most frequent cause of cancer-related death in male and female worldwide, respectively [1]. Esophageal squamous cell carcinoma (ESCC) is the predominant histopathological subtype and comprises up to 90% of esophageal cancer cases worldwide. The incidence of ESCC varies widely by region. The prognosis for ESCC remains poor largely due to late diagnosis and propensity for metastasis. Recent studies have shown that many malignancies contain a cell subpopulation known as cancer stem cells (CSCs), which are thought to cause aggressive tumor behavior and therapy resistance and have high tumor-initiating capacity, thereby leading to recurrence, metastasis, and insufficient response to conventional therapies [6]. CSCs markers that are enriched in ESCC must be determined to isolate cells with stem-like characteristics, improving the prognosis of ESCC patients

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