CCL5 and CCR5 interaction promotes cell motility in human osteosarcoma

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Osteosarcoma exhibits high malignancy and metastatic potential.
• Chemokine ligand 5 (CCL5) is implicated in cancer cell migration and metastasis.
• The role of CCL5 in human osteosarcoma migration and integrin expression remains largely unexplored.

Purpose of the Study:

• To investigate the effect of CCL5 on migration activity and integrin expression in human osteosarcoma cells.
• To elucidate the underlying molecular mechanisms, including receptor involvement and signaling pathways.

Main Methods:

• Assessed CCL5's impact on osteosarcoma cell migration and αvβ3 integrin expression.
• Investigated the role of chemokine receptors CCR5, CCR1, and CCR3.
• Utilized monoclonal antibodies (mAbs), inhibitors, and small interfering RNA (siRNA) to block CCR5 signaling.
• Examined the activation of MEK, ERK, and NF-κB signaling pathways.
• Employed CCL5 shRNA to inhibit endogenous CCL5 expression.

Main Results:

• CCL5 significantly increased migration and αvβ3 integrin expression in osteosarcoma cells.
• CCL5 stimulation upregulated CCR5, but not CCR1 or CCR3.
• Blocking CCR5 with mAb, inhibitor, or siRNA attenuated CCL5-induced migration and integrin upregulation.
• CCL5 activated MEK, ERK, and NF-κB pathways, which were essential for the observed effects.
• Inhibition of these pathways abrogated CCL5-induced migration and integrin expression.
• CCL5 knockdown using shRNA reduced cell migration and integrin expression.

Conclusions:

• The CCL5-CCR5 interaction promotes human osteosarcoma cell migration.
• This process involves the sequential activation of MEK, ERK, and NF-κB signaling pathways.
• The activated signaling cascade leads to the upregulation of αvβ3 integrin, contributing to metastatic potential.