Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, China.
Acta Biomater. 2023 Sep 1;167:436-448. doi: 10.1016/j.actbio.2023.06.011. Epub 2023 Jun 15.
Positive human papillomavirus (HPV) head and neck squamous cell carcinoma (HNSCC) presents a higher risk of lymph node metastasis and poor prognosis. Here, advanced microarray analysis of clinically collected HNSCC tissues revealed significant upregulation of the lncRNA SELL in HPV HNSCC, and its overexpression was obviously associated with lymph node metastasis. The lncRNA SELL could function as a promigratory and proinvasive mediator as well as an inducer of M1-like tumour-associated macrophages (TAM) by increasing the level of L-selectin. Furthermore, fucoidan, as an L-selectin inhibitor, obviously weakened the formation of tongue lesions induced by 4-Nitroquinoline N-oxide (4-NQO) in HPV16 E6/E7 transgenic mice. This result drove us to synchronously develop a nanodelivery platform to verify fucoidan-mediated anti-growth and anti-metastasis effects. This work highlighted the important influence of the lncRNA SELL/L-selectin on promoting HPV HNSCC progression and proposed a potential fucoidan-mediated therapeutic strategy. STATEMENT OF SIGNIFICANCE: Head and neck squamous cell carcinoma (HNSCC) patients with human papillomavirus (HPV) involvement present a greater risk of lymph node metastasis than HPV negative HNSCC patients. However, treatment protocols, including surgery and platinum-based chemo- and radiotherapy, have not improved the 5-year overall survival due to the high tendency of lymphatic metastasis. Here, microarray of clinical HNSCC samples confirms the oncogenic significance of lncRNA SELL, which acts as an M1-like TAM inducer and promotes tumorigenesis by upregulating L-selectin. Fucoidan, as an L-selectin inhibitor, suppresses tongue lesions in transgenic mice, and a fucoidan-mediated nanodelivery platform inhibits HPV HNSCC growth. The present study highlights lncRNA SELL/L-selectin on promoting HPV HNSCC progression and proposes a potential fucoidan-mediated therapeutic.
人乳头瘤病毒（HPV）阳性头颈部鳞状细胞癌（HNSCC）具有更高的淋巴结转移风险和较差的预后。本研究通过对临床收集的 HNSCC 组织进行高级微阵列分析，揭示了 lncRNA SELL 在 HPV HNSCC 中的显著上调，其过表达与淋巴结转移明显相关。lncRNA SELL 可通过增加 L-选择素水平发挥促迁移和促侵袭作用，并诱导 M1 样肿瘤相关巨噬细胞（TAM）。此外，岩藻聚糖硫酸酯作为 L-选择素抑制剂，明显减弱了 HPV16 E6/E7 转基因小鼠中 4-硝基喹啉 N-氧化物（4-NQO）诱导的舌病变的形成。这一结果促使我们同步开发了一种纳米递药平台来验证岩藻聚糖硫酸酯介导的抗生长和抗转移作用。本研究强调了 lncRNA SELL/L-选择素对促进 HPV HNSCC 进展的重要影响，并提出了一种潜在的岩藻聚糖硫酸酯介导的治疗策略。
HPV 阳性的头颈部鳞状细胞癌（HNSCC）患者比 HPV 阴性的 HNSCC 患者发生淋巴结转移的风险更高。然而，由于淋巴结转移的高倾向，包括手术、铂类化疗和放疗在内的治疗方案并未改善 5 年总生存率。本研究通过对临床 HNSCC 样本进行微阵列分析，证实了 lncRNA SELL 的致癌意义，其作为 M1 样 TAM 诱导物，通过上调 L-选择素促进肿瘤发生。岩藻聚糖硫酸酯作为 L-选择素抑制剂，可抑制转基因小鼠的舌病变，岩藻聚糖硫酸酯介导的纳米递药平台可抑制 HPV HNSCC 的生长。本研究强调了 lncRNA SELL/L-选择素在促进 HPV HNSCC 进展中的作用，并提出了一种潜在的岩藻聚糖硫酸酯介导的治疗方法。
