CXCL13 and Its Receptor CXCR5 in Cancer: Inflammation, Immune Response, and Beyond

Abstract

It is well-established that the chemokine C-X-C motif ligand 13 (CXCL13) and its receptor, the G-protein coupled receptor (GPCR) CXCR5, play fundamental roles in inflammatory, infectious and immune responses. Originally identified as a B-cell chemoattractant, CXCL13 exerts important functions in lymphoid neogenesis, and has been widely implicated in the pathogenesis of a number of autoimmune diseases and inflammatory conditions, as well as in lymphoproliferative disorders. Current evidence also indicates that the CXCL13:CXCR5 axis orchestrates cell-cell interactions that regulate lymphocyte infiltration within the tumor microenvironment, thereby determining responsiveness to cytotoxic and immune-targeted therapies. In this review, we provide a comprehensive perspective of the involvement of CXCL13 and its receptor in cancer progression. Studies in recent years postulated novel roles for this chemokine in controlling the cancer cell phenotype, and suggest important functions in the growth and metastatic dissemination of solid tumors. Carcinogens have been found to induce CXCL13 production, and production of this chemokine within the tumor milieu has been shown to impact the proliferation, migration, and invasive properties of cancer cells. Thus, the complex networks of cellular interactions involving tumoral CXCL13 and CXCR5 integrate to promote cancer cell autonomous and non-autonomous responses, highlighting the relevance of autocrine and paracrine interactions in dictating the cancer phenotype. Dissecting the molecular and signaling events regulated by CXCL13 and how this chemokine dynamically controls the interaction between the cancer cell and the tumor microenvironment is key to identify novel effectors and therapeutic targets for cancer treatment.

Chemokine Ligand 13 (CXCL13) in Neuroborreliosis and Neurosyphilis as Selected Spirochetal Neurological Diseases: A Review of Its Diagnostic Significance

“…The chemokine selected as the focus of our review was first described by Legler et al in 1998 [20]. Chemokine ligand 13, also known as B-cell attracting chemokine 1 or B lymphocyte chemoattractant, is a member of the CXC chemokine family encoded by the CXCL13 gene located on chromosome 4 (4q21) [20,21]. CXCL13 in humans is mostly produced by dendritic cells, monocytes, and mature macrophages.…”

CXCL13/CXCR5 Interaction Facilitates VCAM-1-Dependent Migration in Human Osteosarcoma

“…CXCR5 is a specific CXCL13 receptor that mediates CXCL13-regulated cancer functions [ 19 ]. Here, we found that transfecting cells with CXCR5 siRNA reversed the effects of CXCL13 upon cell migration and VCAM-1 expression ( Figure 3 A–C).…”

<p>Targeting Chemokines and Chemokine Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis</p>

“…75 Targeting CXCL13/CXCR5 Axis CXCL13 is a homeostatic chemokine that is continuously expressed in lymphoid tissues, which has a vital role in activating the migration of lymphocytes and antigenpresenting cells. 76,77 Upon binding of CXCL13 to CXCR5, CNS inflammation developed. 78 In MS patients, the levels of CXCL13 were found to be significantly increased and consequently, CXCL13 is considered a biomarker for the disease severity.…”