CCL28-induced RARβ expression inhibits oral squamous cell carcinoma bone invasion

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Oral squamous cell carcinoma (OSCC) bone invasion is linked to poor patient prognosis.
• Understanding the molecular mechanisms regulating OSCC bone metastasis is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of chemokine CCL28 in regulating OSCC bone invasion.
• To explore the potential of CCL28, CCR10, and RARβ as prognostic markers and therapeutic targets for OSCC bone metastasis.

Main Methods:

• In vitro assays examining OSCC cell invasion, epithelial-mesenchymal transition (EMT), and osteoclastogenesis.
• In vivo studies using mouse models of OSCC bone invasion.
• Analysis of CCL28, CCR10, and RARβ expression in patient tumor tissues and correlation with clinical outcomes.

Main Results:

• CCL28 inhibited OSCC cell invasion and EMT by upregulating E-cadherin and downregulating β-catenin.
• CCL28 signaling via CCR10 enhanced retinoic acid receptor-β (RARβ) expression.
• CCL28 reduced RANKL production and osteoclastogenesis, and inhibited tumor growth and osteolysis in vivo.
• Low expression of CCL28, CCR10, and RARβ correlated with increased bone invasion and poorer survival in OSCC patients.

Conclusions:

• CCL28 acts as a negative regulator of OSCC bone invasion.
• CCL28, CCR10, and RARβ are potential biomarkers for predicting OSCC bone invasion and patient survival.
• CCL28 upregulation represents a promising therapeutic strategy for managing OSCC bone metastasis.