Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China.
Special Need Clinic, Hangzhou Stomatology Hospital, Hangzhou, China.
Oral Dis. 2024 May;30(4):2097-2109. doi: 10.1111/odi.14617. Epub 2023 May 30.
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.
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.
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.
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.
口腔鳞状细胞癌（OSCC）常伴有颈部淋巴结转移。间充质干细胞（MSCs）和白细胞介素 6（IL-6）信号被认为在促进肿瘤恶性程度方面发挥重要作用。MSCs 和 IL-6 的详细生物学相互作用及其对 OSCC 转移的后续影响在很大程度上仍不清楚。本研究旨在确定 MSC 衍生的 IL-6 对肿瘤侵袭和转移的影响及其分子机制。
在体外检测 MSC 衍生的 IL-6 和托珠单抗对 OSCC 细胞增殖、迁移和上皮间质转化（EMT）的影响及其潜在途径。此外，还建立了小鼠异种移植模型以体内验证生物学机制。
结果表明，MSCs 和 EMT 相关信号在低分化 OSCC 组织中表达增加。MSCs 释放更高水平的 IL-6，并通过下游分子 JAK 和 STAT3 激活促进 OSCC 细胞的增殖、侵袭和转移以及实体瘤的生长。
结果表明，MSCs 衍生的 IL-6 通过 JAK-STAT3 信号促进肿瘤侵袭和转移。托珠单抗阻断该通路可能是改善 OSCC 患者预后和生存率的一种潜在治疗方法。
