Department of Oral Biology and BK21 PLUS project, Yonsei University College of Dentistry, Seoul, Korea.
Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, Korea.
Eur J Oral Sci. 2021 Feb;129(1):e12750. doi: 10.1111/eos.12750. Epub 2021 Jan 27.
Patients with oral squamous cell carcinoma (OSCC) bone invasion are surgically treated with bone resection, which results in severe physical and psychological damage. Here, we investigated the potential of fractalkine (CX3CL1), which is regulated by transforming growth factor (TGF-β), as a novel biomarker for correct prediction and early detection of OSCC-associated bone invasion. TGF-β knockdown and treatment with a TGF-β-neutralizing antibody decreased the level of fractalkine in the culture media of HSC-2 and YD10B OSCC cells. Treatment with a fractalkine-neutralizing antibody reduced TGF-β-stimulated invasion by HSC-2 and YD10B cells. Fractalkine treatment increased the viability, invasion, and uPA secretion of both OSCC cell lines. Furthermore, OSCC cell bone invasion was assessed following subcutaneous inoculation of wild-type or TGF-β knockdown OSCC cells in mouse calvaria. TGF-β knockdown prevented erosive bone invasion, reduced the number of osteoclasts at the tumor-bone interface, and downregulated fractalkine expression in mouse tumor tissues. Our results indicate that the production of fractalkine is stimulated by TGF-β and mediates TGF-β-induced cell invasion in several OSCC cell lines showing an erosive pattern of bone invasion. Fractalkine may be a useful predictive marker and therapeutic target for OSCC-induced bone destruction.
口腔鳞状细胞癌（OSCC）骨侵袭患者采用骨切除术进行手术治疗，这会导致严重的身体和心理损伤。在这里，我们研究了趋化因子（CX3CL1）的潜力，趋化因子由转化生长因子（TGF-β）调节，作为一种新的生物标志物，用于正确预测和早期检测 OSCC 相关的骨侵袭。TGF-β 敲低和 TGF-β 中和抗体处理降低了 HSC-2 和 YD10B OSCC 细胞培养基中的趋化因子水平。趋化因子中和抗体处理减少了 TGF-β 刺激的 HSC-2 和 YD10B 细胞侵袭。趋化因子处理增加了两种 OSCC 细胞系的活力、侵袭和 uPA 分泌。此外，在小鼠颅骨中皮下接种野生型或 TGF-β 敲低 OSCC 细胞后，评估了 OSCC 细胞的骨侵袭。TGF-β 敲低可防止侵蚀性骨侵袭，减少肿瘤-骨界面处破骨细胞的数量，并下调小鼠肿瘤组织中的趋化因子表达。我们的结果表明，趋化因子的产生受 TGF-β 刺激，并介导几种表现出侵蚀性骨侵袭模式的 OSCC 细胞系中 TGF-β 诱导的细胞侵袭。趋化因子可能是 OSCC 诱导骨破坏的有用预测标志物和治疗靶点。
