Tumor-Associated Macrophage-Derived CXCL1 Promotes Endometrial Cancer Progression Through the CXCR2/NF-κB Pathway

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Advanced-stage and metastatic endometrial cancer (EC) have poor survival rates.
• Tumor-associated macrophages (TAMs), especially M2 subtype, promote EC progression but mediators are unclear.
• The CXCL1/CXCR2 axis role in TAM-driven EC progression requires investigation.

Purpose of the Study:

• To investigate the role of C-X-C motif chemokine ligand 1 (CXCL1) and chemokine receptor 2 (CXCR2) in TAM-induced EC progression.
• To elucidate the CXCL1/CXCR2 signaling pathway in EC metastasis.
• To evaluate the therapeutic potential of targeting the CXCL1/CXCR2 axis in EC.

Main Methods:

• Investigated CXCL1 and CXCR2 roles in EC progression using in vitro and in vivo models.
• Utilized CXCR2 silencing and NF-κB inhibitor (BAY 11-7082) to block signaling.
• Analyzed CXCL1, CXCR2, and macrophage infiltration in human EC tissue samples.

Main Results:

• CXCL1/CXCR2 axis activation promotes EC proliferation, migration, and epithelial-mesenchymal transition via NF-κB signaling.
• CXCR2 inhibition or CXCL1 neutralization reduced TAM-driven EC progression in xenograft models.
• Elevated CXCL1, CXCR2, and macrophage infiltration correlated significantly with advanced EC stage and poor prognosis.

Conclusions:

• The CXCL1/CXCR2 axis is a key mediator of TAM-induced EC progression and metastasis.
• Targeting the CXCL1/CXCR2 pathway presents a promising therapeutic strategy for advanced EC.
• CXCL1 and CXCR2 expression levels may serve as prognostic biomarkers for EC.