Signaling via the CXCR5/ERK pathway is mediated by CXCL13 in mice with breast cancer

Abstract

Breast cancer is the most common cause of cancer-associated mortality and the most frequently diagnosed type of cancer in women worldwide. It has been revealed that the chemokine C-X-C motif chemokine ligand 13 (CXCL13) serves a pivotal role in breast cancer growth and is associated with lymph node metastasis. However, to the best of our knowledge, the mechanism by which CXCL13 mediates breast cancer growth remains uncharacterized. Female BALB/c mice were used in this study. Tumor volume was calculated and changes of gross tumor morphology were observed by hematoxylin and eosin staining. The expression of CXCL13, C-X-C motif chemokine receptor 5 (CXCR5) and extracellular signaling-related kinase (ERK) mRNA and protein expression were detected by reverse transcriptase quantitative-polymerase chain reaction and western blot analysis. Simultaneously, the production of cytokines [interleukin-1β (IL-1β), tumor necrosis factor (TNF) and tumor growth factor β1 (TGF-β1)] was detected by an ELISA. The CXCL13 inhibitor reduced tumor volume and growth, and reduced the mRNA and protein expression levels of key members of the CXCR5/ERK signaling pathway: CXCL13, CXCR5 and ERK. Furthermore, the detectable concentration of the cytokines IL-1β and TNF decreased following CXCL13 inhibition, whereas the concentration of TGF-β1 was increased. The attenuation of tumor growth resulting from CXCL13 inhibition may be associated with the CXCR5/ERK signaling pathway. This study provides a theoretical basis for treating breast cancer through CXCL13 inhibition in clinical trials.