{"doi":"10.3390/cancers15215168","title":"Heparan-6-O-Endosulfatase 2 Promotes Invasiveness of Head and Neck Squamous Carcinoma Cell Lines in Co-Cultures with Cancer-Associated Fibroblasts","abstract":"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 cucumber Holothuria 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.","journal":"Cancers","year":2023,"id":358778,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":650358,"name":"Xin Zhou","orcid":"0000-0002-0480-3068","position":1,"is_corresponding":false},{"id":325659,"name":"Július Benický","orcid":"0000-0002-1941-1622","position":2,"is_corresponding":false},{"id":979201,"name":"Aswini Panigrahi","orcid":"0009-0006-3111-9030","position":3,"is_corresponding":false},{"id":1109142,"name":"Reem Aljuhani","orcid":"0009-0000-1466-1238","position":4,"is_corresponding":false},{"id":288986,"name":"Jian Liu","orcid":"0000-0001-8552-1400","position":5,"is_corresponding":false},{"id":378820,"name":"Laurie Ailles","orcid":"0000-0001-7289-8882","position":6,"is_corresponding":false},{"id":789006,"name":"Vitor H. Pomin","orcid":"0000-0002-5015-8880","position":7,"is_corresponding":false},{"id":342592,"name":"Zhangjie Wang","orcid":"0000-0003-4301-953X","position":8,"is_corresponding":false},{"id":325663,"name":"Radoslav Goldman","orcid":"0000-0003-1304-0522","position":9,"is_corresponding":false},{"id":1109141,"name":"Pritha Mukherjee","orcid":"0000-0001-6573-4580","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:13:48.379546Z","pmid":"37958342","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}