{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T11:06:55Z","timestamp":1779534415716,"version":"3.53.1"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Guangdong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2021A1515010252"],"award-info":[{"award-number":["2021A1515010252"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303240"],"award-info":[{"award-number":["82303240"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8227032897"],"award-info":[{"award-number":["8227032897"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172637"],"award-info":[{"award-number":["82172637"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002402","name":"Sun Yat-sen University","doi-asserted-by":"publisher","award":["R08044"],"award-info":[{"award-number":["R08044"]}],"id":[{"id":"10.13039\/501100002402","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Letters"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.canlet.2026.218462","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T16:09:09Z","timestamp":1774714149000},"page":"218462","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Blocking CEMIP2-mediated low-molecular-weight hyaluronic acid -TGF\u03b2 signaling inhibits chemotherapy-associated lymphatic metastasis in gastric cancer"],"prefix":"10.1016","volume":"649","author":[{"given":"Huanjie","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinbo","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahuang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongman","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoxiong","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haobin","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfa","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafeng","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinming","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.canlet.2026.218462_bib1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41568-020-00300-6","article-title":"Cancer progression and the invisible phase of metastatic colonization","volume":"20","author":"Klein","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.canlet.2026.218462_bib2","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2021.18457","article-title":"Global incidence and mortality of gastric cancer, 1980-2018","volume":"4","author":"Wong","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"10.1016\/j.canlet.2026.218462_bib3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13045-023-01451-3","article-title":"Gastric cancer treatment: recent progress and future perspectives","volume":"16","author":"Guan","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.canlet.2026.218462_bib4","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ijsu.2018.01.008","article-title":"Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. Meta-analysis of randomized trials","volume":"51","author":"Coccolini","year":"2018","journal-title":"Int. J. Surg."},{"key":"10.1016\/j.canlet.2026.218462_bib5","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s10120-023-01404-2","article-title":"Neoadjuvant chemotherapy in older patients with gastric cancer undergoing surgery: a population-based cohort study","volume":"26","author":"Keywani","year":"2023","journal-title":"Gastric Cancer"},{"key":"10.1016\/j.canlet.2026.218462_bib6","doi-asserted-by":"crossref","first-page":"413","DOI":"10.3390\/genes1030413","article-title":"Programming pluripotent precursor cells derived from Xenopus embryos to generate specific tissues and organs","volume":"1","author":"Borchers","year":"2010","journal-title":"Genes"},{"key":"10.1016\/j.canlet.2026.218462_bib7","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nrclinonc.2016.128","article-title":"Does the mobilization of circulating tumour cells during cancer therapy cause metastasis?","volume":"14","author":"Martin","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218462_bib8","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aan0026","article-title":"Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism","volume":"9","author":"Karagiannis","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.canlet.2026.218462_bib9","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/s41556-018-0256-3","article-title":"Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models","volume":"21","author":"Keklikoglou","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.canlet.2026.218462_bib10","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1158\/2159-8290.CD-24-0002","article-title":"The interplay between extracellular matrix remodeling and cancer therapeutics","volume":"14","author":"Prakash","year":"2024","journal-title":"Cancer Discov."},{"key":"10.1016\/j.canlet.2026.218462_bib11","first-page":"1","article-title":"Emerging roles for hyaluronidase in cancer metastasis and therapy","volume":"123","author":"McAtee","year":"2014","journal-title":"Adv. Cancer Res."},{"key":"10.1016\/j.canlet.2026.218462_bib12","doi-asserted-by":"crossref","first-page":"43094","DOI":"10.1074\/jbc.M112.349209","article-title":"The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering","volume":"287","author":"Yang","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2026.218462_bib13","doi-asserted-by":"crossref","first-page":"32259","DOI":"10.1074\/jbc.M300347200","article-title":"Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells","volume":"278","author":"Sugahara","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2026.218462_bib14","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1136\/gutjnl-2012-302529","article-title":"Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer","volume":"62","author":"Jacobetz","year":"2013","journal-title":"Gut"},{"key":"10.1016\/j.canlet.2026.218462_bib15","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1172\/JCI97712","article-title":"MAPK4 overexpression promotes tumor progression via noncanonical activation of AKT\/mTOR signaling","volume":"129","author":"Wang","year":"2019","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.canlet.2026.218462_bib16","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jconrel.2013.08.014","article-title":"Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles","volume":"172","author":"Kooijmans","year":"2013","journal-title":"J. Contr. Release"},{"key":"10.1016\/j.canlet.2026.218462_bib17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.matbio.2017.02.003","article-title":"Hyaluronan modulates growth factor induced mammary gland branching in a size dependent manner","volume":"63","author":"Tolg","year":"2017","journal-title":"Matrix Biol."},{"key":"10.1016\/j.canlet.2026.218462_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2024.133744","article-title":"Hyaluronic acid as a tumor progression agent and a potential chemotherapeutic biomolecule against cancer: a review on its dual role","volume":"275","author":"Gagneja","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.canlet.2026.218462_bib19","doi-asserted-by":"crossref","DOI":"10.3390\/biom10030487","article-title":"TGF-beta signaling","volume":"10","author":"Tzavlaki","year":"2020","journal-title":"Biomolecules"},{"key":"10.1016\/j.canlet.2026.218462_bib20","doi-asserted-by":"crossref","DOI":"10.3390\/biom11121850","article-title":"CD44: a multifunctional mediator of cancer progression","volume":"11","author":"Hassn Mesrati","year":"2021","journal-title":"Biomolecules"},{"key":"10.1016\/j.canlet.2026.218462_bib21","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.matbio.2018.03.020","article-title":"TMEM2: a missing link in hyaluronan catabolism identified?","volume":"78\u201379","author":"Yamaguchi","year":"2019","journal-title":"Matrix Biol."},{"key":"10.1016\/j.canlet.2026.218462_bib22","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.2147\/IJN.S231214","article-title":"Exosome-delivered c-Met siRNA could reverse chemoresistance to cisplatin in gastric cancer","volume":"15","author":"Zhang","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"10.1016\/j.canlet.2026.218462_bib23","unstructured":"Functional exosome-mimic for Delivery of Sirna to Cancer: in Vitro and in Vivo Evaluation."},{"key":"10.1016\/j.canlet.2026.218462_bib24","article-title":"NPR1 promotes lipid droplet lipolysis to enhance mitochondrial oxidative phosphorylation and fuel gastric cancer metastasis","volume":"12","author":"Fu","year":"2025","journal-title":"Adv. Sci. (Weinh.)"},{"key":"10.1016\/j.canlet.2026.218462_bib25","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.3892\/mmr.2017.6419","article-title":"iRGD as a tumor-penetrating peptide for cancer therapy","volume":"15","author":"Yin","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.canlet.2026.218462_bib26","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/cac2.12518","article-title":"Engineered extracellular vesicles: a new approach for targeted therapy of tumors and overcoming drug resistance","volume":"44","author":"Ming\u2010Kun","year":"2023","journal-title":"Cancer Commun."},{"key":"10.1016\/j.canlet.2026.218462_bib27","first-page":"423","article-title":"Superiority of the 8th edition of the TNM staging system for predicting overall survival in gastric cancer: comparative analysis of the 7th and 8th editions in a monoinstitutional cohort","volume":"9","author":"Wang","year":"2018","journal-title":"Mol. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218462_bib28","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.1158\/0008-5472.CAN-19-1147","article-title":"Chemotherapy-induced metastasis: molecular mechanisms, clinical manifestations, therapeutic interventions","volume":"79","author":"Karagiannis","year":"2019","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2026.218462_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2025.217898","article-title":"CEMIP2 sensitizes PDAC to chemotherapy through extracellular matrix remodeling by hyaluronan degradation","volume":"630","author":"Yao","year":"2025","journal-title":"Cancer Lett."},{"key":"10.1016\/j.canlet.2026.218462_bib30","unstructured":"TMEM2 is a SOX4 Regulated Gene that Mediates Metastatic Migration and Invasion in Breast Cancer."},{"key":"10.1016\/j.canlet.2026.218462_bib31","doi-asserted-by":"crossref","first-page":"5679","DOI":"10.2147\/IJN.S383862","article-title":"Combined self-assembled iRGD polymersomes for effective targeted siRNA anti-tumor therapy","volume":"17","author":"Li","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"10.1016\/j.canlet.2026.218462_bib32","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/bjc.2014.332","article-title":"Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid correlates with lymphatic invasion and lymph node metastasis","volume":"111","author":"Schmaus","year":"2014","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.canlet.2026.218462_bib33","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2016.1232235","article-title":"Low-molecular-weight hyaluronan (LMW-HA) accelerates lymph node metastasis of melanoma cells by inducing disruption of lymphatic intercellular adhesion","volume":"5","author":"Du","year":"2016","journal-title":"OncoImmunology"},{"key":"10.1016\/j.canlet.2026.218462_bib34","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.devcel.2019.04.018","article-title":"High-molecular-weight hyaluronan is a hippo pathway ligand directing cell density-dependent growth inhibition via PAR1b","volume":"49","author":"Ooki","year":"2019","journal-title":"Dev. Cell"},{"key":"10.1016\/j.canlet.2026.218462_bib35","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1200\/JCO.20.00590","article-title":"Randomized phase III trial of pegvorhyaluronidase alfa with nab-paclitaxel plus gemcitabine for patients with Hyaluronan-High metastatic pancreatic adenocarcinoma","volume":"38","author":"Van Cutsem","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218462_bib36","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.tranon.2018.10.003","article-title":"Subcutaneous inoculation of 3D pancreatic cancer spheroids results in development of reproducible stroma-rich tumors","volume":"12","author":"Durymanov","year":"2019","journal-title":"Transl. Oncol."},{"key":"10.1016\/j.canlet.2026.218462_bib37","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1002\/stem.30","article-title":"Identification of gastric cancer stem cells using the cell surface marker CD44","volume":"27","author":"Takaishi","year":"2009","journal-title":"Stem Cell."},{"key":"10.1016\/j.canlet.2026.218462_bib38","doi-asserted-by":"crossref","first-page":"28670","DOI":"10.18632\/oncotarget.8764","article-title":"A reciprocal regulatory circuit between CD44 and FGFR2 via c-myc controls gastric cancer cell growth","volume":"7","author":"Park","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.canlet.2026.218462_bib39","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1046\/j.1523-1747.2001.00236.x","article-title":"CD44 is the principal mediator of hyaluronic-acid-induced melanoma cell proliferation","volume":"116","author":"Ahrens","year":"2001","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.canlet.2026.218462_bib40","doi-asserted-by":"crossref","first-page":"5797","DOI":"10.1038\/s41467-022-33598-x","article-title":"Chemotherapy-induced complement signaling modulates immunosuppression and metastatic relapse in breast cancer","volume":"13","author":"Monteran","year":"2022","journal-title":"Nat. Commun."}],"container-title":["Cancer Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526002259?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526002259?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T10:57:56Z","timestamp":1779533876000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0304383526002259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":40,"alternative-id":["S0304383526002259"],"URL":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218462","relation":{},"ISSN":["0304-3835"],"issn-type":[{"value":"0304-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Blocking CEMIP2-mediated low-molecular-weight hyaluronic acid -TGF\u03b2 signaling inhibits chemotherapy-associated lymphatic metastasis in gastric cancer","name":"articletitle","label":"Article Title"},{"value":"Cancer Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218462","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"218462"}}