{"doi":"10.1016/j.ebiom.2021.103685","title":"A lymphatic co-culture model for personalized cancer medicine","abstract":"Head and neck squamous carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, throat, and larynx, and the majority of HNSCC patients develop lymph node metastasis which is correlated with poor prognoses and increased risk of distant metastasis [[1]Warburton G Nikitakis NG Roberson P et al.Histopathological and lymphangiogenic parameters in relation to lymph node metastasis in early stage oral squamous cell carcinoma.J Oral Maxillofac Surg. 2007; 65: 475-484Summary Full Text Full Text PDF PubMed Scopus (57) Google Scholar]. Undoubtedly, there is an urgent need to decipher biological and biophysical factors underlying the lymphatic metastasis to prevent tumor spread. Tumor lymphangiogenesis involves remodeling of pre-existing lymphatic vessels to be more permeable as well as formation of new lymphatic vessels from the existing vessels, which are considered as a favor entry of cancer cells into the lymphatic system [[2]Lee E Pandey NB Popel AS. Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment.Expert Rev Mol Med. 2015; 17: e3Crossref PubMed Scopus (49) Google Scholar]. There is also growing evidence highlighting tumor microenvironment (TME) contribution to HNSCC progression. For example, TME in HNSCC is characterized by highly complex and heterogeneous stroma consisting of cancer associated fibroblasts (CAFs) that have been shown to induce lymph node metastasis in HNSCC [[3]Wheeler SE Shi H Lin F et al.Enhancement of head and neck squamous cell carcinoma proliferation, invasion, and metastasis by tumor-associated fibroblasts in preclinical models.Head Neck. 2014; 36: 385-392Crossref PubMed Scopus (68) Google Scholar]. To understand crosstalk between CAFs and lymph node metastasis, it is critical to create model systems that allow to dissect the molecular pathways between them, and to identify individualized targets to treat patients when taking the HNSCC tumor heterogeneity into consideration as the heterogeneity leads to inconsistencies in patients’ drug responses. In this issue of EBioMedicine, Lugo-Cintrón and colleagues investigated the roles of HNSCC patient tumor derived fibroblasts in lymphangiogenesis in vitro using a three-dimensional (3D) microfluidic system [[4]Lugo-Cintron KM Ayuso JM Humayun M et al.Primary Head and Neck Tumour-Derived Fibroblasts Promote Lymphangiogenesis in a Lymphatic Organotypic Co-culture Model.EBioMedicine. 2021; 73103634Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar]. In general, 3D microfluidic systems consist of multiple compartments and cells embedded in extracellular matrix (ECM) with biophysical and biochemical cues mimicking multicellular tumor architecture, bridging the gap between conventional 2D cell culture and animal models [[5]Sontheimer-Phelps A Hassell BA Ingber DE. Modelling cancer in microfluidic human organs-on-chips.Nat Rev Cancer. 2019; 19: 65-81Crossref PubMed Scopus (278) Google Scholar,[6]Lee E Song HG Chen CS. Biomimetic on-a-chip platforms for studying cancer metastasis.Curr Opin Chem Eng. 2016; 11: 20-27Crossref PubMed Scopus (33) Google Scholar]. In their study, Lugo-Cintrón and colleagues investigated fibroblast-induced alterations in lymphatic endothelial gene expression using their lymphatic coculture model to understand the heterogeneity of HNSCC and predict potentially effective treatments for inhibiting tumor lymphangiogenesis [[4]Lugo-Cintron KM Ayuso JM Humayun M et al.Primary Head and Neck Tumour-Derived Fibroblasts Promote Lymphangiogenesis in a Lymphatic Organotypic Co-culture Model.EBioMedicine. 2021; 73103634Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar]. They utilized previously developed 3D microfluidic system with a single hollow cylindrical channel embedded in an extracellular matrix [[7]Henderson AR Ilan IS Lee E. A bioengineered lymphatic vessel model for studying lymphatic endothelial cell-cell junction and barrier function","journal":"EBioMedicine","year":2021,"id":208981,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":796141,"name":"Esak Lee","orcid":"0000-0002-5328-6677","position":1,"is_corresponding":false},{"id":796612,"name":"Anna M. Kolarzyk","orcid":null,"position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T23:52:01.526969Z","pmid":"34753105","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":[]}