{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:38:46Z","timestamp":1786358326046,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CHE 2227874"],"award-info":[{"award-number":["CHE 2227874"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CHE 2227874"],"award-info":[{"award-number":["CHE 2227874"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Galectin-3-mediated processes are important during many aspects of cancer progression, but they are not well understood. Galectin-3 is present extracellularly, and because of its carbohydrate recognition domain (CRD) and unstructured N-terminal domain (NTD), galectin-3 undergoes multimerization, which influences events such as carbohydrate-controlled cell\u2013cell interactions. Investigations reported herein using an in vitro wound-healing assay show that exogenous galectin-3 inhibits cancer cellular migration. Since the addition of the galectin-3 CRD without the NTD does not arrest cellular migration, we attribute the effect of full-length galectin-3 on migration to the extracellular interactions between multimeric, full-length galectin-3 and extracellular receptors. In this publication, lactose-functionalized dendrimers serve as multivalent binding partners for galectin-3 and are used to mitigate extracellular multivalent galectin\/carbohydrate interactions. The addition of lactose-functionalized dendrimers provides significant restoration of cellular migration in the presence of exogenous galectin-3 without increasing cellular viability. Thus, although galectin-3\/protein interactions within the cell are known to increase both cellular migration and viability, cell surface galectin-3\/carbohydrate interactions have the opposite impact and decrease cellular migration.<\/jats:p>","DOI":"10.3390\/ijms27167145","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:23:50Z","timestamp":1786357430000},"page":"7145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Galectin-3\/Carbohydrate Interactions Modulate Cancer Cellular Migration"],"prefix":"10.3390","volume":"27","author":[{"given":"Mackenzie S.","family":"Fricke","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramat S.","family":"Tahir","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5562-0967","authenticated-orcid":false,"given":"Hazal K.","family":"Ural","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary J.","family":"Cloninger","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1021\/bi201459p","article-title":"The Carbohydrate-Binding Site in Galectin-3 Is Preorganized To Recognize a Sugarlike Framework of Oxygens: Ultra-High-Resolution Structures and Water Dynamics","volume":"51","author":"Saraboji","year":"2012","journal-title":"Biochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sciacchitano, S., Lavra, L., Morgante, A., Ulivieri, A., Magi, F., De Francesco, G.P., Bellotti, C., Salehi, L.B., and Ricci, A. (2018). Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020379"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ahmed, R., Anam, K., and Ahmed, H. (2023). Development of Galectin-3 Targeting Drugs for Therapeutic Applications in Various Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098116"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40364-025-00759-1","article-title":"Multifaceted roles of Galectins: From carbohydrate binding to targeted cancer therapy","volume":"13","author":"Zhang","year":"2025","journal-title":"Biomark. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1074\/jbc.M606862200","article-title":"Galectin-3 interaction with Thomsen-Friedenreich disaccharide on cancer-associated MUC1 causes increased cancer cell endothelial adhesion","volume":"282","author":"Yu","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1002\/cbic.201402134","article-title":"Lactose-Functionalized Dendrimers Arbitrate the Interaction of Galectin-3\/MUC1 Mediated Cancer Cellular Aggregation","volume":"15","author":"Michel","year":"2014","journal-title":"ChemBioChem"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4030","DOI":"10.1021\/acs.bioconjchem.8b00599","article-title":"Chemoenzymatic Synthesis of Galectin Binding Glycopolymers","volume":"29","author":"Ennist","year":"2018","journal-title":"Bioconj. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8487","DOI":"10.1021\/jacs.5c19731","article-title":"Structural Heterogeneity and Hydrodynamics of an Intrinsically Disordered Protein Condensate","volume":"148","author":"Carrick","year":"2026","journal-title":"J. Am. Chem. Soc."},{"key":"ref_9","unstructured":"Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., and Prestegard, J.H. (2022). Galectins. Essentials of Glycobiology, Cold Spring Harbor Laboratory Press. [4th ed.]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1023\/B:GLYC.0000014082.99675.2f","article-title":"Extracellular functions of galectin-3","volume":"19","author":"Ochieng","year":"2002","journal-title":"Glycoconj. J."},{"key":"ref_11","first-page":"509","article-title":"How galectins have become multifunctional proteins","volume":"35","author":"Caballero","year":"2020","journal-title":"Histol. Histopathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6086","DOI":"10.1158\/1078-0432.CCR-18-3870","article-title":"Impact of Galectins in Resistance to Anticancer Therapies","volume":"26","author":"Navarro","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.canlet.2011.09.003","article-title":"Galectin-3-A jack-of-all-trades in cancer","volume":"313","author":"Newlaczyl","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.bbamcr.2015.08.008","article-title":"Galectin 3 as a guardian of the tumor microenvironment","volume":"1863","author":"Ruvolo","year":"2016","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/glycob\/cwu086","article-title":"Galectin-3 in angiogenesis and metastasis","volume":"24","author":"Funasaka","year":"2014","journal-title":"Glycobiology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41573-023-00636-2","article-title":"Targeting galectin-driven regulatory circuits in cancer and fibrosis","volume":"22","author":"Marino","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1093\/glycob\/cwy001","article-title":"Galectin-3 and cancer stemness","volume":"28","author":"Hogan","year":"2018","journal-title":"Glycobiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s10585-011-9376-x","article-title":"Transient silencing of galectin-3 expression promotes both in vitro and in vivo drug-induced apoptosis of human pancreatic carcinoma cells","volume":"28","author":"Kobayashi","year":"2011","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1053\/j.gastro.2009.09.061","article-title":"Galectin-3 Increases Gastric Cancer Cell Motility by Up-regulating Fascin-1 Expression","volume":"138","author":"Kim","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1074\/jbc.M209590200","article-title":"MDA-MB-435 human breast carcinoma cell homo- and heterotypic adhesion under flow conditions is mediated in part by Thomsen-Friedenreich antigen-galectin-3 interactions","volume":"278","author":"Khaldoyanidi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_21","first-page":"101","article-title":"Adhesion of human breast carcinoma to extracellular matrix proteins is modulated by galectin-3","volume":"17","author":"Warfield","year":"1997","journal-title":"Invasion Metastasis"},{"key":"ref_22","first-page":"3805","article-title":"Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium","volume":"63","author":"Glinsky","year":"2003","journal-title":"Cancer Res."},{"key":"ref_23","first-page":"3117","article-title":"Galectin-3 expression alters adhesion, motility and invasion in a lung cell line (DLKP), in vitro","volume":"22","author":"Linehan","year":"2002","journal-title":"Anticancer Res."},{"key":"ref_24","first-page":"e13072","article-title":"The apoptotic effect of resveratrol in ovarian cancer cells is associated with downregulation of galectin-3 and stimulating miR-424-3p transcription","volume":"43","author":"Shati","year":"2019","journal-title":"J. Food Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1002\/ijc.25946","article-title":"Transient gene silencing of galectin-3 suppresses pancreatic cancer cell migration and invasion through degradation of \u03b2-catenin","volume":"129","author":"Kobayashi","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26577","DOI":"10.1038\/srep26577","article-title":"Galectin-3 Enhances Migration of Minature Pig Bone Marrow Mesenchymal Stem Cells Through Inhibition of RhoA-GTP Activity","volume":"6","author":"Gao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11010-015-2584-y","article-title":"Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells","volume":"411","author":"Shetty","year":"2016","journal-title":"Mol. Cell. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1295\/polymj.17.117","article-title":"A New Class of Polymers\u2014Starburst-Dendritic Macromolecules","volume":"17","author":"Tomalia","year":"1985","journal-title":"Polym. J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tomalia, D.A., and Durst, H.D. (1993). Genealogically Directed Synthesis: Starburst\/Cascade Dendrimers and Hyperbranched Structures, Springer.","DOI":"10.1002\/chin.199334313"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Newkome, G.R., Moorefield, C.N., and V\u00f6gtle, F. (2001). Dendrimers and Dendrons: Concepts, Syntheses, Applications, Wiley-VCH.","DOI":"10.1002\/3527600612"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.3762\/bjoc.10.162","article-title":"Multivalent scaffolds induce galectin-3 aggregation into nanoparticles","volume":"10","author":"Goodman","year":"2014","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105400","DOI":"10.1016\/j.jbc.2023.105400","article-title":"The Universe of Galectin-Binding Partners and Their Functions in Health and Disease","volume":"299","author":"Troncoso","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1093\/glycob\/9.11.1253","article-title":"Lactose-containing starburst dendrimers: Influence of dendrimer generation and binding-site orientation of receptors (plant\/animal lectins and immunoglobulins) on binding properties","volume":"9","author":"Andre","year":"1999","journal-title":"Glycobiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0065-2318(10)63006-5","article-title":"Design and creativity in synthesis of multivalent neoglycoconjugates","volume":"63","author":"Chabre","year":"2010","journal-title":"Adv. Carbohydr. Chem. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/S0076-6879(03)01016-4","article-title":"Comparative studies of galactoside-containing clusters","volume":"Volume 362","author":"Liu","year":"2003","journal-title":"Methods in Enzymology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1590\/S1984-82502013000700008","article-title":"Glycodendrimers: Versatile tools for nanotechnology","volume":"49","author":"Roy","year":"2013","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7666","DOI":"10.1039\/C5PY01283J","article-title":"Multifaceted glycodendrimers with programmable bioactivity through convergent, divergent, and accelerated approaches using polyfunctional cyclotriphosphazenes","volume":"6","author":"Abbassi","year":"2015","journal-title":"Polym. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1021\/ol802613r","article-title":"Probing the Lactose center dot GM3 Carbohydrate-Carbohydrate Interaction with Glycodendrimers","volume":"11","author":"Seah","year":"2009","journal-title":"Org. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1021\/acs.biomac.3c00426","article-title":"Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding: Increased Glycan Affinity to Galectins Correlates with Aggregation Behavior","volume":"24","author":"Hamala","year":"2023","journal-title":"Biomacromolecules"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/1439-7633(20011105)2:11<822::AID-CBIC822>3.0.CO;2-W","article-title":"Wedgelike glycodendrimers as inhibitors of binding of mammalian galectins to glycoproteins, lactose maxiclusters, and cell surface glycoconjugates","volume":"2","author":"Andre","year":"2001","journal-title":"ChemBioChem"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1039\/b210923a","article-title":"Rigidified multivalent lactose molecules and their interactions with mammalian galectins; a route to selective inhibitors","volume":"1","author":"Vrasidas","year":"2003","journal-title":"Org. Biomol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1021\/acs.biomac.8b00168","article-title":"Terminal Sugar Moiety Determines Immunomodulatory Properties of Poly(propyleneimine) Glycodendrimers","volume":"19","author":"Gorzkiewicz","year":"2018","journal-title":"Biomacromolecules"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1039\/D2CS00736C","article-title":"Multivalent glycosystems for human lectins","volume":"52","author":"Rojo","year":"2023","journal-title":"Chem. Soc. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7985","DOI":"10.1021\/acs.biomac.4c01245","article-title":"Systematic Evaluation of Macromolecular Carbohydrate-Lectin Recognition Using Precision Glycopolymers","volume":"25","author":"Williams","year":"2024","journal-title":"Biomacromolecules"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1186\/s12951-025-03422-x","article-title":"Automatic target-seeking nanoparticle inhibiting orthotopic drug-resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferation","volume":"23","author":"Bai","year":"2025","journal-title":"J. Nanobiotech."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/ijc.2910210305","article-title":"Isolation of a human prostate carcinoma cell line (DU 145)","volume":"21","author":"Stone","year":"1978","journal-title":"Int. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/1097-0142(197404)33:4<1027::AID-CNCR2820330419>3.0.CO;2-Z","article-title":"Characterization of a newly derived human sarcoma cell line (HT-1080)","volume":"33","author":"Rasheed","year":"1974","journal-title":"Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"29017","DOI":"10.1021\/acsomega.0c03416","article-title":"Time-Dependent Fluorescence Spectroscopy to Quantify Complex Binding Interactions","volume":"5","author":"Bernhard","year":"2020","journal-title":"ACS Omega"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1039\/D4MA00782D","article-title":"The toxicity, uptake, and impact on galectin-3 mediated apoptosis of lactose functionalized PAMAM dendrimers","volume":"6","author":"Fricke","year":"2025","journal-title":"Mat. Adv."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1002\/(SICI)1521-3773(19981102)37:20<2754::AID-ANIE2754>3.0.CO;2-3","article-title":"Polyvalent interactions in biological systems: Implications for design and use of multivalent ligands and inhibitors","volume":"37","author":"Mammen","year":"1998","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_51","unstructured":"Gale, J.W.S.a.P.A. (2012). Multivalency in Supramolecular Chemistry: From Molecules to Nanomaterials, John Wiley & Sons Ltd."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1002\/anie.200502794","article-title":"Synthetic multivalent ligands as probes of signal transduction","volume":"45","author":"Kiessling","year":"2006","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1073\/pnas.68.8.1678","article-title":"Entropic contributions to rate accelerations in enzymic and intramolecular reactions and chelate effect","volume":"68","author":"Page","year":"1971","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5649","DOI":"10.1158\/0008-5472.CAN-10-1040","article-title":"AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective","volume":"70","author":"Talmadge","year":"2010","journal-title":"Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Fortuna-Costa, A., Gomes, A.M., Kozlowski, E.O., Stelling, M.P., and Pavao, M.S. (2014). Extracellular galectin-3 in tumor progression and metastasis. Front. Oncol., 4.","DOI":"10.3389\/fonc.2014.00138"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1023\/B:GLYC.0000014084.01324.15","article-title":"Galectin-3 and metastasis","volume":"19","author":"Takenaka","year":"2004","journal-title":"Glycoconj. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.1039\/D0PY00667J","article-title":"Protein aggregation nucleated by functionalized dendritic polyglycerols","volume":"11","author":"Bernhard","year":"2020","journal-title":"Polym. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"106516","DOI":"10.1016\/j.pep.2024.106516","article-title":"CUREs for high-level Galectin-3 expression","volume":"221","author":"Charbonneau","year":"2024","journal-title":"Protein Expr. Purif."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7145\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:25:24Z","timestamp":1786357524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,9]]},"references-count":58,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167145"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167145","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,9]]}}}