CD163 as a marker of M2 macrophage, contribute to predict aggressiveness and prognosis of Kazakh esophageal squamous cell carcinoma

Abstract

M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of esophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163 and CD34 as the marker of M2 macrophages and endothelial cells, were used to identify the M2 macrophages density and microvessel density, respectively. Immunohistochemistry staining was evaluated the expression of MMP9. The number of infiltrated CD163-positive M2 macrophages in tumor islets and stroma was significantly higher than in cancer adjacent normal tissues. The increased of M2 macrophages and microvessel density were significantly correlated with more malignant phenotypes including lymph node metastasis and clinical stage progression. Meanwhile, the expression of MMP9 showed much higher level in esophageal squamous cell carcinoma than that in cancer adjacent normal tissues, and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was significantly associated with age, depth of tumor invasion, lymph node metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor stroma was positively associated with microvessel density and the expression of MMP9, and as an independent poorly prognostic factor for overall survival time of Kazakh esophageal squamous cell carcinoma. These findings suggest the increased number of M2 macrophages correlated with high expression of MMP9 and high microvessel density may contribute to the tumor aggressiveness and angiogenesis, promoting the progression of Kazakh esophageal squamous cell carcinoma.

IL‐1β from M2 macrophages promotes migration and invasion of ESCC cells enhancing epithelial‐mesenchymal transition and activating NF‐κB signaling pathway

“…In the present investigation, to understand the association between the infiltration of M2 macrophages and metastasis of ESCC, relevant literatures were meta‐analyzed. To confirm in our own cases, the infiltration of M2 macrophages in ESCC was evaluated using immunohistochemistry with CD163, a well‐accepted specific surface marker of M2 macrophages . Meta‐analysis revealed that the infiltration of M2 macrophages was markedly associated with lymph node metastasis, clinical stage and T classification in ESCC.…”

“…To confirm in our own cases, the infiltration of M2 macrophages in ESCC was evaluated using immunohistochemistry with CD163, a well-accepted specific surface marker of M2 macrophages. 6 Meta-analysis revealed that the infiltration of M2 macrophages was markedly associated with lymph node metastasis, clinical stage and T classification in ESCC. In our own cases, M2 macrophages were shown to be predominantly infiltrated in ESCC relative to normal controls.…”

MCP2 activates NF‐κB signaling pathway promoting the migration and invasion of ESCC cells

“…Macrophages comprise the most abundant population of immune cells in the TME and can undergo differentiation into functional phenotypes depending on the local tissue environment. Presence of M2 macrophages and a high ratio of M2/M1 macrophages in the TME have been reported to be clinically linked with poor prognosis in many types of cancers, including ESCC (Shigeoka et al, 2013;Hu et al, 2017). Presence of M2 macrophages and a high ratio of M2/M1 macrophages in the TME have been reported to be clinically linked with poor prognosis in many types of cancers, including ESCC (Shigeoka et al, 2013;Hu et al, 2017).…”

“…On the basis of these functional phenotypes, tumor-associated macrophages (TAMs) can either promote (M2 subtype) or prevent (M1 type) tumor progression (Zheng et al, 2017). Presence of M2 macrophages and a high ratio of M2/M1 macrophages in the TME have been reported to be clinically linked with poor prognosis in many types of cancers, including ESCC (Shigeoka et al, 2013;Hu et al, 2017). However, the mechanism by which M2 macrophages promote the malignant behaviors of cancer cells remains elusive.…”

Chronic inflammation in skeletal muscle impairs satellite cells function during regeneration: can physical exercise restore the satellite cell niche?

“…M2 macrophages are activated by IL‐4 and IL‐13, and have anti‐inflammatory properties, by producing cytokines such as IL‐10 . Also, M2 macrophages express Arg1, cluster of differentiation 163 (CD163), and mannose receptor (CD206) .…”