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

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.

A Role of CXCL1 Drives Osteosarcoma Lung Metastasis via VCAM-1 Production

“…Cell adhesion molecules play critical roles during the extravasation step, a situation where cancer cells adhere to the vasculature endothelium of small capillaries and then migrate through the vasculature wall to generate metastatic foci of tumor metastasis ( 32 ), but few known in human osteosarcoma. Previous studies suggested that VCAM-1-dependent motility is an essential factor for tumor metastatic developments ( 33 , 34 ). To investigate tumor metastatic developments, the role of VCAM-1 in CXCL1 upon osteosarcoma cell migration was examined.…”

“…NF-κB has been demonstrated as a crucial factor for cancer cell migration and invasion ( 33 , 37 , 38 ). The NF-κB luciferase promoter plasmid was used for evaluating the possibility of CXCL1-mediated CXCR2/FAK/PI3K/Akt pathway on NF-κB expression.…”

“…Chemokines have pro-inflammatory functions and play various roles in regulations of cell activation, differentiation, adhesion, and trafficking in immune cells involved in reprogramming of somatic cells to pluripotent stem cells (39)(40)(41). Moreover, upregulations of chemokines to facilitate proliferation and manage apoptosis, survival, and metastasis in several types of cancer are observed (10,33).…”

Identification of Driver Genes and Key Pathways of Osteosarcoma Shows K-7174 As a Novel Anti-osteosarcoma Drug by Inhibiting VCAM1

“…In previous study, upregulation of VCAM-1 was observed to increase the migration of osteosarcoma cell [32]. Further study showed that CXCL13/CXCR5 axis activation facilitates the production of VCAM-1 via NF-kb pathway [33]. Thus, VCAM1 might be target of osteosarcoma progression and metastasis.…”

Osteoporosis: From Molecular Mechanisms to Therapies 2.0

“…The study researchers hypothesize the reasons for this signaling disparity and they call for further analysis into this BMP signaling cascade, as this might reveal opportunities to design more effective therapeutics [5]. Liu et al, indicated that the migration and metastasis of abnormal osteoblasts (osteosarcomas) is regulated by CXCL3/CXCR5 interaction [6].…”