M2 Macrophages Secrete CXCL13 to Promote Renal Cell Carcinoma Migration, Invasion, and EMT

Abstract

Objective: M2 macrophages are associated with a poor prognosis in a variety of malignancies. There are, however, few relevant investigations in clear cell renal cell carcinoma (ccRCC).Methods: The expression of M2 macrophages in ccRCC tissues was first discovered using immunohistochemistry in this study. Then, M2 macrophages were created in vitro to see how they affected the proliferation, migration, invasion, and EMT of ccRCC cells. Using qPCR and prognostic analysis identifies important chemokine. Antibody neutralization tests confirmed the chemokine’s involvement and function. Pathway inhibitors confirmed the main pathway of M2 macrophages in ccRCC. Finally, qPCR and IHC were used to confirm the expression of chemokine receptors in ccRCC tissues.Results: The presence of M2 macrophages was linked to a poor outcome in ccRCC. M2 macrophages enhanced the proliferation, migration, invasion, and EMT of ccRCC lines in vitro. CXCL13 was identified as the main chemokine by prognostic analysis and qPCR tests. CXCL13 neutralizing antibodies can inhibit the stimulation of M2 macrophages in ccRCC lines’ proliferation, migration, invasion, and EMT. M2 macrophages and CXCL13 may activate the Akt pathway in ccRCC lines, and Akt inhibitors decrease ccRCC lines proliferation, migration, invasion, and EMT. CXCR5 expression is a poor prognostic factor for renal cell carcinoma, according to qPCR and immunohistochemistry. In vivo experiments further proved that CXCL13 secreted by M2 macrophages can promote tumor proliferation.Conclusion: M2 macrophages in the immunological milieu secrete CXCL13, which promotes ccRCC proliferation, migration, invasion, and EMT. Our findings contribute to a better understanding of the function of the tumor microenvironment in the incidence and progression of ccRCC, and they may point to novel therapeutic targets for ccRCC.

Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma

“…M2 macrophages create an environment conducive to tumor survival by releasing growth factors, chemokines, and other inflammatory mediators (Solinas et al, 2009;Lin et al, 2019). In addition, M2 macrophages can also promote tumor metastasis and invasion by promoting angiogenesis and other pathways (Jetten et al, 2014;Xie et al, 2021). To further analyze the differences in composition and function within M2 macrophages, we used bioinformatics to perform an in-depth analysis at the single cell level.…”

Autophagy-related gene LAPTM4B promotes the progression of renal clear cell carcinoma and is associated with immunity

“…M2 macrophages are essential in the occurrence and development of ccRCC. M2 macrophages can enhance the proliferation, migration, invasion, and EMT of ccRCC cells in an Akt-dependent manner by secreting CXCL13 (Xie et al, 2021). The negative correlation (Table 1) between LAPTM4B and most immune checkpoints partially explained the insensitivity of ccRCC to immunotherapy, this evidence suggested that LAPTM4B may promote the growth and metastasis of renal cancer by boosting the immune escape of tumor cells.…”

Integrated Analysis of the Role of Enolase 2 in Clear Cell Renal Cell Carcinoma

“…Over the years, M2 macrophages have been reported to exert an immunosuppressive function in multiple cancers [26]. For example, Xie et al [27] demonstrated that M2 macro-phages could secrete chemokine (C-X-C motif) ligand 13 to promote ccRCC migration, invasion, and EMT. Martínez et al [28] showed that overexpression of bone morphogenetic protein 4 could induce polarization of M2 macrophages, thereby facilitating proliferation, invasion, and migration of bladder cancer cells.…”