Abstract
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.
Highlights
Osteosarcoma is the most common primary bone tumor and is highly malignant [1]
We found that CXCL13 levels were upregulated in the high-migration-prone sublines (Figure 1E,F)
Transfecting MG-63 cells with CXCL13 siRNA did not significantly affect cell proliferation (Figure S1). These results indicate that CXCL13 promotes human osteosarcoma cell migration
Summary
Neoadjuvant and adjuvant chemotherapy for osteosarcoma has largely remained unchanged since the 1980s, with wide surgical excision and preservation of limb function [1]. Despite such treatment, only 60–70% of patients without clinically evident metastasis at first diagnosis remain alive after 3 years [2]. Since the lung is the most frequent organ affected by metastasis in osteosarcoma [2], the development of therapeutic strategies for delaying or inhibiting lung metastasis progression remains critical for improving patient survival outcomes. The metastatic process is a multi-stage cascade, whereby cancer characterized by the dissemination of tumor cells with proteolytic activity, enabling the tumor to invade various tissues [1]. Inhibiting VCAM-1 expression may be an effective strategy for treating osteosarcoma metastasis
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