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Review | Open Access

The biological role of the CXCL12/CXCR4 axis in esophageal squamous cell carcinoma

Xianxian Wu1,*, Hongdian Zhang1,*, Zhilin Sui1, Yang Wang2, Zhentao Yu1 ( )
Departments of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China

*These authors contributed equally to this work.

Show Author Information

Abstract

Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) is the main histological type of esophageal cancer, and accounts for 90% of all cancer cases. Despite the progress made in surgery, chemotherapy, and radiotherapy, the mortality rate from esophageal cancer remains high, and the overall 5-year survival rate is less than 20%, even in developed countries. The C-X-C motif chemokine ligand 12 (CXCL12) is a member of the CXC chemokine subgroup, which is widely expressed in a variety of tissues and cells. CXCL12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor, C-X-C motif chemokine receptor type 4 (CXCR4), where it causes embryonic development, immune response, and angiogenesis. In addition, increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor cells. Studies have shown that CXCL12 and its receptor, CXCR4, are highly expressed in ESCC. This abnormal expression contributes to tumor proliferation, lymph node and distant metastases, and worsening prognosis. At present, antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of tumors. This article summarizes the structure, function, and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of ESCC. Current results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.

Keywords

Esophageal squamous cell carcinomaantagonistsC-X-C motif chemokine ligand 12CXC chemokine receptor 4imaging agent

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Cancer Biology & Medicine
Volume 18 Issue 2,
May 2021
Pages 401-410
DOI: 10.20892/j.issn.2095-3941.2020.0140
Cite this article:
Wu X, Zhang H, Sui Z, et al. The biological role of the CXCL12/CXCR4 axis in esophageal squamous cell carcinoma. Cancer Biology & Medicine, 2021, 18(2): 401-410. https://doi.org/10.20892/j.issn.2095-3941.2020.0140

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Received: 27 March 2020
Accepted: 30 July 2020
Published: 01 May 2021
©2021 Cancer Biology & Medicine.

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