Objectives: Oral squamous cell carcinoma (OSCC) is often diagnosed with cervical lymph node metastasis. Mesenchymal stem cells (MSCs) and interleukin-6 (IL-6) signalling are considered to play important roles in promoting tumour malignancy. The detailed biological interaction of MSCs and IL-6 and the subsequent effect on OSCC metastasis remain largely unclear. This study aimed to determine the effects and molecular mechanism of MSCs-derived IL-6 on tumour invasion and metastasis.
Subjects and methods: The effects of MSC-derived IL-6 and tocilizumab on the proliferation, mobility, and epithelial-mesenchymal transition (EMT) of OSCC cells and potential pathways were detected in vitro. In addition, a murine xenograft model was generated to verify the biological mechanism in vivo.
Results: The results showed that the expression of MSCs and EMT-related signals was increased in poorly differentiated OSCC tissues. MSCs released a higher level of IL-6 and promoted the proliferation, invasion, and metastasis of OSCC cells and solid neoplasms, which were activated by the downstream molecules JAK and STAT3.
Conclusions: The results indicated that MSCs-derived IL-6-promoted tumour invasion and metastasis via JAK-STAT3 signalling. Blockade of this pathway by tocilizumab may be a potential treatment to improve the prognosis and survival rate of patients with OSCC.
Keywords: cancer progression; interleukin 6; mesenchymal stem cell; metastasis; oral squamous cell carcinoma.
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