Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients

Abstract

The abilities of chemokines in orchestrating cellular migration are utilised by different (patho-)biological networks including malignancies. However, except for CXCR4/CXCL12, little is known about the relation between tumour-related chemokine expression and the development and progression of solid tumours like breast cancer. In this study, microarray analyses revealed the overexpression of chemokine CXCL13 in breast cancer specimens. This finding was confirmed by real-time polymerase chain reaction in a larger set of samples (n ¼ 34) and cell lines, and was validated on the protein level performing Western blot, ELISA, and immunohistochemistry. Levels of CXCR5, the receptor for CXCL13, were low in malignant and healthy breast tissues, and surface expression was not detected in vitro. However, we observed a strong (P ¼ 0.0004) correlation between the expressions of CXCL13 and CXCR5 in breast cancer tissues, indicating a biologically relevant role of CXCR5 in vivo. Finally, we detected significantly elevated serum concentrations of CXCL13 in patients with metastatic disease (n ¼ 54) as compared with controls (n ¼ 44) and disease-free patients (n ¼ 48). In conclusion, CXCL13 is overexpressed within breast cancer tissues, and increased serum levels of this cytokine can be found in breast cancer patients with metastatic disease pointing to a role of CXCL13 in the progression of breast cancer, suggesting that CXCL13 might serve as a useful therapeutic target and/or diagnostic marker in this malignancy.

A Novel Function of CXCL13 to Stimulate RANK Ligand Expression in Oral Squamous Cell Carcinoma Cells

“…Therefore, RANKL expression in OSCC cells could be regulated through complex autocrine transcriptional regulatory mechanisms operative in tumor cells. Recently, it has been shown that CXCL13 is overexpressed in tumor tissues and in peripheral blood of breast cancer patients (27). Thus, our findings that CXCL13 stimulates RANKL expression implicate a novel function of CXCL13 in the tumor osteolytic process and in metastasis.…”

CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma

“…CXCL13 concentration in CSF was also elevated in 6 of 11 subjects with CNS demyelinating disease (9-116 pg/mL), consistent with previous observations. 25 Of note, CXCL13 concentration was also elevated in the CSF of 3 of 6 patients with breast cancer metastatic to the brain (58-508 pg/mL), suggesting a role for this chemokine in directional migration of breast cancer cells to the brain 26 (Table 1; supplemental Tables 1-3). We noted that newly diagnosed patients with CNS involvement of lymphoma (both primary and secondary) with low CSF levels of CXCL13 at diagnosis (below the median concentration of 200 pg/mL) exhibited significantly longer progression-free survival (PFS) with standardized treatment 27 compared with newly diagnosed patients with high CSF CXCL13, suggesting a physiological role for this chemokine in CNS lymphoma pathogenesis ( Figure 2).…”

CD4+ follicular helper T cell infiltration predicts breast cancer survival

“…CXCL13 mRNA expression in tumor sections was recently shown to predict survival of patients with BC, particularly in the HER2 + subtype, although the cell source was not identified (38). An earlier study suggested tumor cells were the major CXCL13 producers in BC but their IHC protocol used higher concentrations of a monoclonal antibody that intensely labeled most cells, both in the tumor tissue and the LN control (39). In contrast, our IHC experiments, using lower concentrations of a polyclonal antibody, stained only some GC-located cells in the LN control, the tumor-associated TLS, and the occasional intratumoral lymphocyte (Supplemental Figure 4C), suggesting that CXCL13 production by tumor cells needs to be reexamined.…”