文章：

肝素-6-O-内硫酸酯酶2在与癌症相关成纤维细胞共培养中促进头颈部鳞状细胞癌细胞系的侵袭性

Heparan-6-O-Endosulfatase 2 Promotes Invasiveness of Head and Neck Squamous Carcinoma Cell Lines in Co-Cultures with Cancer-Associated Fibroblasts

原文发布日期：27 October 2023

DOI: 10.3390/cancers15215168

类型: Article

开放获取: 是

英文摘要：

Local invasiveness of head and neck squamous cell carcinoma (HNSCC) is a complex phenomenon supported by interaction of the cancer cells with the tumor microenvironment (TME). We and others have shown that cancer-associated fibroblasts (CAFs) are a component of the TME that can promote local invasion in HNSCC and other cancers. Here we report that the secretory enzyme heparan-6-O-endosulfatase 2 (Sulf-2) directly affects the CAF-supported invasion of the HNSCC cell lines SCC35 and Cal33 into Matrigel. The Sulf-2 knockout (KO) cells differ from their wild type counterparts in their spheroid growth and formation, and the Sulf-2-KO leads to decreased invasion in a spheroid co-culture model with the CAF. Next, we investigated whether a fucosylated chondroitin sulfate isolated from the sea cucumberHolothuria floridana(HfFucCS) affects the activity of the Sulf-2 enzyme. Our results show that HfFucCS not only efficiently inhibits the Sulf-2 enzymatic activity but, like the Sulf-2 knockout, inhibits Matrigel invasion of SCC35 and Cal33 cells co-cultured with primary HNSCC CAF. These findings suggest that the heparan-6-O-endosulfatases regulate local invasion and could be therapeutically targeted with the inhibitory activity of a marine glycosaminoglycan.

摘要翻译： 

头颈部鳞状细胞癌（HNSCC）的局部侵袭性是一种复杂的现象，其发生依赖于癌细胞与肿瘤微环境（TME）的相互作用。我们及其他研究团队已证实，癌症相关成纤维细胞（CAFs）作为TME的组成部分，能够促进HNSCC及其他癌症的局部侵袭。本研究发现，分泌型酶类硫酸乙酰肝素-6-O-内硫酸酯酶2（Sulf-2）直接影响CAFs支持的HNSCC细胞系SCC35和Cal33对基质胶的侵袭能力。与野生型细胞相比，Sulf-2基因敲除（KO）细胞在球体生长和形成方面存在差异，且在与CAFs共培养的球体模型中，Sulf-2敲除导致细胞侵袭能力下降。进一步研究显示，从海参佛罗里达海参中分离的岩藻糖基化硫酸软骨素（HfFucCS）能够影响Sulf-2酶活性。实验结果表明，HfFucCS不仅能有效抑制Sulf-2酶活性，而且与Sulf-2敲除类似，可抑制原代HNSCC CAFs共培养条件下SCC35和Cal33细胞对基质胶的侵袭。这些发现表明，硫酸乙酰肝素-6-O-内硫酸酯酶家族调控局部侵袭过程，而海洋来源的糖胺聚糖抑制剂可能成为该酶系的潜在治疗靶向策略。

原文链接：

Heparan-6-O-Endosulfatase 2 Promotes Invasiveness of Head and Neck Squamous Carcinoma Cell Lines in Co-Cultures with Cancer-Associated Fibroblasts