Mesenchymal stem cells‐derived IL‐6 promotes invasion and metastasis of oral squamous cell carcinoma via JAK‐STAT3 signalling

• Published in: Oral diseases Vol. 30; no. 4; pp. 2097 - 2109
• Main Authors: Liu, Chuanxia, Zhou, Jinhan, Zhang, Shanshan, Fu, Ji, Li, Yining, Hao, Yilong, Yuan, Jian, Tang, Fan, Ge, Weili, He, Hong, Chen, Qianming
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.05.2024
• Subjects: Animals; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; cancer progression; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - secondary; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cytokines; Epithelial-Mesenchymal Transition; Female; Humans; Interleukin 6; Interleukin-6 - metabolism; Janus Kinases - metabolism; Lymph nodes; Male; Malignancy; Medical diagnosis; Medical prognosis; mesenchymal stem cell; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Metastases; Metastasis; Mice; Mice, Nude; Molecular modelling; Monoclonal antibodies; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Neoplasm Invasiveness; Neoplasm Metastasis; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Signal Transduction; Squamous cell carcinoma; Stat3 protein; STAT3 Transcription Factor - metabolism; Stem cells; Survival analysis; Tumors; Xenografts; interleukin 6; mesenchymal stem cell; oral squamous cell carcinoma; cancer progression; metastasis
• ISSN: 1354-523X; 1601-0825; 1601-0825
• DOI: 10.1111/odi.14617

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.