Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 21, Issue 17, Pages -Publisher
MDPI
DOI: 10.3390/ijms21176095
Keywords
CXCL13; CXCR5; migration; invasion; osteosarcoma
Funding
- Ministry of Science and Technology of Taiwan [MOST 107-2320-B-039-019-MY3, MOST-108-2314-B-039-034-MY3, 106-2314-B-341-001-MY3]
- China Medical University [CMU109-ASIA-01]
- Shin-Kong Wu Ho-Su Memorial Hospital [108-SKH-FJU-06]
- Chang Gung Medical Research Program Foundation [CMRPF6K0041]
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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 (PLC beta), protein kinase C alpha (PKC alpha), c-Src, and nuclear factor-kappa B (NF-kappa B) signaling pathways. CXCL13 and CXCR5 appear to be a novel therapeutic target in metastatic osteosarcoma.
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