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Tumour invasion and migration within lymphatics remain incompletely defined, yet likely co-opt immune-cell physiological programs for accessing lymphatic capillaries during surveillance and inflammation resolution. Lymphatic entry is discussed as directional migration, adhesion and junctional remodeling, with emphasis on hyaluronan (HA)–LYVE-1 and CD44 signaling in lymphatic entry and nodal metastasis.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/lymphatic-trafficking-of-immune-cells-and-insights-for-cancer-metastasis/406537/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/lymphatic-trafficking-of-immune-cells-and-insights-for-cancer-metastasis/406537.png","ImageObject",300,407,{"name":92,"@type":93},"A glass of water","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How do most cancers spread via the lymphatic system?","Question",{"text":113,"@type":114},"They metastasize through lymphatics to draining lymph nodes, which can then enable systemic dissemination after invasion into high endothelial venules in the paracortex.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What molecular features guide and enable immune cells to enter lymphatic vessels?",{"text":118,"@type":114},"Immune-cell entry involves directional guidance (chemotaxis, haptotaxis, durotaxis), adhesion to vessel surfaces through receptors such as integrins, and junctional remodeling involving MMPs and ADAMs.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is the HA–LYVE-1 and CD44 axis important for lymphatic entry and metastasis?",{"text":122,"@type":114},"The review highlights hyaluronan interacting with LYVE-1 on lymphatic endothelium and with CD44 on incoming immune cells, supporting a mechanism for lymphatic entry that may also assist tumour nodal metastasis. In vivo studies show LYVE-1 or CD44 disruption reduces immune-cell trafficking and downstream immune responses.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},406537,1790887349,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":29,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962090760832,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Clinical & Experimental Metastasis (2024) 41:381–386 [https://doi.org/10.1007/s10585-023-10229-3](https://doi.org/10.1007/s10585-023-10229-3)  \nREVIEW  \nLymphatic trafficking of immune cells and insights for cancer metastasis  \nDavid G. Jackson1  \nReceived: 15 May 2023 / Accepted: 28 July 2023 / Published online: 22 August 2023 © The Author(s) 2023  \nAbstract  \nMost cancers and in particular carcinomas metastasise via the lymphatics to draining lymph nodes from where they can potentially achieve systemic dissemination by invasion of high endothelial blood venules (HEVs) in the paracortex [1, 2] . Currently however, the mechanisms by which tumours invade and migrate within the lymphatics are incompletely understood, although it seems likely they exploit at least some of the normal physiological mechanisms used by immune cells to access lymphatic capillaries and traffic to draining lymph nodes in the course of immune surveillance, immune modulation and the resolution of inflammation [3, 4] . Typically these include directional guidance via chemotaxis, haptotaxis and durotaxis, adhesion to the vessel surface via receptors including integrins, and junctional re-modelling by MMPs (Matrix MetalloProteinases) and ADAMs (A Disintegrin And Metalloproteinases) [5–7] . This short review focusses on a newly emerging mechanism for lymphatic entry that involves the large polysaccharide hyaluronan (HA) and its key lymphatic and immune cell receptors respectively LYVE-1 (Lymphatic Vessel Endothelial receptor) and CD44, and outlines recent work which indicates this axis may also be used by some tumours to aid nodal metastasis.  \nKeywords Lymphatic · Immune cell · Tumour metastasis · LYVE-1 · Hyaluronan · Glycocalyx  \nArticle  \nThe majority of immune cells that traffic from peripheral tissues to afferent lymphatics effect their entry within the first 200 μm of initial blind-ended capillaries at the distinctive overlapping junctions between the oakleaf shaped endothelial cells [5] . Here, and to a certain extent in adjoining lymphatic pre-collectors the interdigitating membrane flaps of such cells are “buttoned” at their sides by the adherens-junction protein VE-cadherin (Vascular Endothelialcadherin) and tight junction proteins including Claudin-5,  \nPresented at the 9th International Congress on Cancer Metastasis through the Lymphovascular System, May 4–6, 2023, in San Francisco, CA. To be published in a Special Issue of Clinical and Experimental Metastasis: Molecular Mechanisms of Cancer Metastasis.  \n􀀍 David G. Jackson [David.jackson@imm.ox.ac.uk](David.jackson@imm.ox.ac.uk)  \n1 Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK  \nZO-1 (Zonula Occludens-1), ESAM (Endothelial Selective Adhesion Molecule) and JAM-A (Junctional Adhesion Molecule-A), while their tips are lined with PECAM-1 (Platelet Endothelial Cell Adhesion Molecule-1, CD31), and the lymphatic endothelial HA receptor LYVE-1 [5, 8– 10] to form discrete junctional “portals” of approximately 0.5–1 μm through which individual immune cells can enter by pushing and squeezing [5, 11–14] . As predicted from its location in such portals, we recently demonstrated that LYVE-1 plays a key role in the entry of antigen presenting Dendritic cells (DCs) and macrophages to initial capillaries by engaging with its ligand HA, anchored in the surface glycocalyx of the incoming immune cells by the closely related leucocyte receptor CD44 [15–17] . This role ofLYVE-1 has similarities to the one played by CD44 in mediating the exit of T cells from inflamed blood capillaries. There however, the HA glycocalyx is present on the (luminal) endothelium, where it serves to capture activated circulating T cells (which also express CD44 but lack an HA coat) by forming a CD44:HA:CD44 sandwich [18–20] . Synthesized primarily by HA synthase-2 (HAS2) in DCs and macrophages, thenascent HA chains associate with CD44 in intracellular vesicles, fr","cbCaijo23cYRKQkx","https://ap.wps.com/l/cbCaijo23cYRKQkx","pdf",2490645,"English","# Abstract\n## Lymphatic entry pathways and immune cell trafficking\n## HA–LYVE-1 and CD44 mechanisms in lymphatic access\n## Evidence from in vivo models and functional implications","[{\"question\":\"How do most cancers spread via the lymphatic system?\",\"answer\":\"They metastasize through lymphatics to draining lymph nodes, which can then enable systemic dissemination after invasion into high endothelial venules in the paracortex.\"},{\"question\":\"What molecular features guide and enable immune cells to enter lymphatic vessels?\",\"answer\":\"Immune-cell entry involves directional guidance (chemotaxis, haptotaxis, durotaxis), adhesion to vessel surfaces through receptors such as integrins, and junctional remodeling involving MMPs and ADAMs.\"},{\"question\":\"Why is the HA–LYVE-1 and CD44 axis important for lymphatic entry and metastasis?\",\"answer\":\"The review highlights hyaluronan interacting with LYVE-1 on lymphatic endothelium and with CD44 on incoming immune cells, supporting a mechanism for lymphatic entry that may also assist tumour nodal metastasis. In vivo studies show LYVE-1 or CD44 disruption reduces immune-cell trafficking and downstream immune responses.\"}]","Lymphatic trafficking of immune cells and insights for cancer metastasis | PDF",1790566288,15]