CXCL5/CXCR2 axis in tumor microenvironment as potential diagnostic biomarker and therapeutic target

Abstract

The components of the tumor microenvironment (TME) in solid tumors, especially chemokines, are currently attracting much attention from scientists. C-X-C motif chemokine ligand 5 (CXCL5) is one of the important chemokines in TME. Overexpression of CXCL5 is closely related to the survival time, recurrence and metastasis of cancer patients. In TME, CXCL5 binds to its receptors, such as C-X-C motif chemokine receptor 2 (CXCR2), to participate in the recruitment of immune cells and promote angiogenesis, tumor growth, and metastasis. The CXCL5/CXCR2 axis can act as a bridge between tumor cells and host cells in TME. Blocking the transmission of CXCL5/CXCR2 signals can increase the sensitivity and effectiveness of immunotherapy and slow down tumor progression. CXCL5 and CXCR2 are also regarded as biomarkers for predicting prognosis and molecular targets for customizing the treatment. In this review, we summarized the current literature regarding the biological functions and clinical significance of CXCL5/CXCR2 axis in TME. The possibility to use CXCL5 and CXCR2 as potential prognostic biomarkers and therapeutic targets in cancer is also discussed

CXCL5 Has Potential to Be a Marker for Hepatocellular Carcinoma Prognosis and Was Correlating With Immune Infiltrates

“…There are many reports on the mechanism of CXCL5 promoting cancer progression. The combination of CXCL5 and CXCR2 exerts a strong granulocyte chemotaxis and angiogenesis effect, and CXCL5/CXCR2 axis plays an important role in mediating the infiltration and metastasis of malignant tumors ( 8 ). Recently, the CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis ( 24 ).…”

“…CXCL5 is secreted by epithelial cells, endothelial cells, immune cells, etc. and recognized and combined with the G protein coupled receptor CXCR2 ( 8 ). It can recognize and bind to CXCR2, and perform many cellular functions including adhesion, invasion, and diffusion through autocrine or non-autocrine pathways, thus affecting the growth, proliferation, metastasis, and invasion of tumors.…”

Role of Chemokines in the Biology of Cholangiocarcinoma

“…CXCL5, also known as epithelial-derived neutrophil-activating peptide-78 (ENA-78) is secreted by inflammatory and endothelial cells of various organs in response to insults [ 2 ]. Binding to its receptors, such as CXCR2, which is expressed in neutrophils, monocytes, eosinophils, endothelial cells and others [ 88 ], CXCL5 participates in immune cell recruitment, promotes angiogenesis and is involved in tumor progression [ 187 ]. In tumors, the CXCL5/CXCR2 axis has been implicated in multiple processes, as angiogenesis, growth, metastasis and chemoresistance, acting on TME, cancer stem cells and immune checkpoints [ 188 ].…”

Fibroblasts in cancer dormancy: foe or friend?

“…CAFs were the main source of chemokines such as CXCL5 [ 50 ] and CXCL1 [ 51 ]. The addition of exogenous recombinant CXCL5 protein could promote the proliferation of quiescent breast cancer cells under healthy bone co-cultures via binding to CXCR2 [ 52 ].…”