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

• Published in: International journal of molecular sciences 2020-08, Vol.21 (17), p.6095
• Main Authors: Liu, Ju-Fang, Lee, Chiang-Wen, Lin, Chih-Yang, Chao, Chia-Chia, Chang, Tsung-Ming, Han, Chien-Kuo, Huang, Yuan-Li, Fong, Yi-Chin, Tang, Chih-Hsin
• Format: Article
• Language: English
• Subjects: Apoptosis; Binding sites; Biomedical materials; Bone cancer; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Breast cancer; Cancer therapies; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell growth; Cell Movement - genetics; Chemokine CXCL13 - metabolism; Chemokine CXCL13 - physiology; Chemokines; CXCL13; CXCL13 protein; CXCR5; CXCR5 protein; Humans; invasion; Kinases; Metastases; Metastasis; migration; Motility; Neoplasm Invasiveness - genetics; NF-κB protein; Osteosarcoma; Osteosarcoma - genetics; Osteosarcoma - metabolism; Osteosarcoma - pathology; Osteosarcoma cells; Phospholipase; Phospholipase C; Phosphorylation; Protein Binding; Protein kinase C; Receptors, CXCR5 - metabolism; Receptors, CXCR5 - physiology; Sarcoma; Signal Transduction - physiology; siRNA; Src protein; Tumor Cells, Cultured; Vascular cell adhesion molecule 1; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21176095

Osteosarcoma is the most common primary tumor of the skeletal system and is well-known to have an aggressive clinical outcome and high metastatic potential. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays a vital role in the development of several cancers. However, the effect of CXCL13 in the motility of osteosarcoma cells remains uncertain. Here, we found that CXCL13 increases the migration and invasion potential of three osteosarcoma cell lines. In addition, CXCL13 expression was upregulated in migration-prone MG-63 cells. Vascular cell adhesion molecule 1 (VCAM-1) siRNA and antibody demonstrated that CXCL13 promotes migration via increasing VCAM-1 production. We also show that CXCR5 receptor controls CXCL13-mediated VCAM-1 expression and cell migration. Our study identified that CXCL13/CXCR5 axis facilitate VCAM-1 production and cell migration in human osteosarcoma via the phospholipase C beta (PLCβ), protein kinase C α (PKCα), c-Src, and nuclear factor-κB (NF-κB) signaling pathways. CXCL13 and CXCR5 appear to be a novel therapeutic target in metastatic osteosarcoma.