Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea.
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.
FASEB J. 2021 Jan;35(1):e21181. doi: 10.1096/fj.202001455R. Epub 2020 Nov 24.
Head and neck squamous cell carcinoma (HNSCC) metastasizes to the locoregional lymph nodes at high rates and is related to poor clinical outcomes. However, the mechanism by which cancer cells migrate to the lymph nodes is unclear. To address this, we established a conditioned medium culture system for HNSCC cells and lymphatic endothelial cells (LECs) and investigated their crosstalk. Stimulation with tumor-conditioned medium (TCM) activated LECs, resulting in a robust increase in cell proliferation to induce lymphatic hyperplasia. Further, stimulation of HNSCC cells with activated LEC Conditioned media (TCM-LEC CM) induced cell invasion. Among various chemokines, CXCL5 promoted the invasion of TCM-LEC CM-treated HNSCC cells. The level of CXCL5 protein was higher in cancer tissues than those in normal tissues from HNSCC patients. Furthermore, treatment with SB225002, a CXCR2 (CXCL5 receptor) inhibitor, resulted in decreased lymph node metastasis in vivo. In conclusion, inhibition of CXCL5-CXCR2 signaling between cancer cells and LECs suppresses cancer cell invasion and metastasis in vitro and in vivo. This novel therapeutic strategy might be a practical approach to the clinical management of HNSCC.
头颈部鳞状细胞癌（HNSCC）转移至局部区域淋巴结的比率很高，与不良的临床结局相关。然而，癌细胞向淋巴结转移的机制尚不清楚。为了解决这个问题，我们建立了 HNSCC 细胞和淋巴管内皮细胞（LEC）的条件培养基培养系统，并研究了它们之间的串扰。肿瘤条件培养基（TCM）刺激激活了 LEC，导致细胞增殖显著增加，从而诱导淋巴管增生。此外，用激活的 LEC 条件培养基（TCM-LEC CM）刺激 HNSCC 细胞诱导细胞侵袭。在各种趋化因子中，CXCL5 促进了 TCM-LEC CM 处理的 HNSCC 细胞的侵袭。与 HNSCC 患者的正常组织相比，癌症组织中的 CXCL5 蛋白水平更高。此外，用 CXCR2（CXCL5 受体）抑制剂 SB225002 治疗，导致体内淋巴结转移减少。总之，抑制癌细胞和 LEC 之间的 CXCL5-CXCR2 信号通路可抑制体外和体内的癌细胞侵袭和转移。这种新的治疗策略可能是 HNSCC 临床管理的一种实用方法。
