Similarities between wound re-epithelialization and Metastasis in ESCC and the crucial involvement of macrophages: A review

Abstract

In cancer, tumor-associated macrophages (TAMs) possess crucial functions in facilitating epithelial-mesenchymal transition (EMT). EMT is a crucial process in tumor metastasis. Tumor metastasis is one of the hallmarks of cancer and leads to patient mortality. Cancer cells often find ways to evade being detected and attacked by the immune system. This is achieved by cross-talk between cancer cells and the altered microenvironment. The accumulation of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) creates an immunosuppressive and tumor-supportive environment. Circulating monocytes and macrophages which are recruited into tumors are defined as tumor-associated macrophages once in the TME. Based on the activated stimuli and function, macrophages can be divided into M1 macrophages and M2 macrophages. M1 macrophages, also known as classically activated macrophages, exhibit pro-inflammatory and antitumor activities. M2 macrophages, also known as alternatively activated macrophages, exhibit anti-inflammatory, pro-tumorigenic, and wound healing activities. TAMs are considered to be of the M2 phenotype. The TME polarizes recruited macrophages into M2 macrophages as they provide an immunosuppressive pro-tumoral environment. Accumulating studies show that the presence of TAMs in esophageal squamous cell carcinoma (ESCC) leads to tumor progression. In this review, we discuss how EMT can be used by TAMs to cause tumor migration and metastasis in ESCC. We also discuss the potential therapies targeting TAMs.

Keywords: Esophageal Squamous cell Carcinoma. M1 and M2 macrophages. Tumor-associated macrophages. Re-epithelialization. Epithelial-mesenchymal transition. Metastasis. Migration. Vimentin. E-cadherin. Transforming growth factor-β.