{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T13:22:36Z","timestamp":1770297756025,"version":"3.49.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T00:00:00Z","timestamp":1540857600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T00:00:00Z","timestamp":1540857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The physiological importance of the interactions between hyaluronic acid (HA) and its main membrane receptor, CD44, in pathological processes, e.g. cancer, is well recognized. However, these interactions are mainly studied in solution, whereas HA in the extracellular matrix (ECM) is partially immobilized via its interactions with other ECM components. We therefore, developed substrates in which HA is presented in an ECM-relevant manner. We immobilized HA with different molecular weights (M<jats:sub>w<\/jats:sub>) in a Layer-by-Layer (LbL) fashion and studied the interactions of the substrates with CD44 and two human gastric cancer cell lines that overexpress this receptor, namely AGS and MKN45. We demonstrate that MKN45 cells are more sensitive to the LbL substrates as compared with AGS. This difference is due to different CD44 expression: while CD44 is detected mainly in the cytoplasm of AGS, MKN45 express CD44 predominantly at the cell membrane where it is involved in the recognition and binding of HA. The invasiveness of the studied cell lines was also evaluated as a function of HA M<jats:sub>w<\/jats:sub>. Invasive profile characterized by low cell adhesion, high cell motility, high expression of cortactin, formation of invadopodia and cell clusters was observed for MKN45 cells when they are in contact with substrates presenting HA of high M<jats:sub>w<\/jats:sub>.<\/jats:p>","DOI":"10.1038\/s41598-018-34445-0","type":"journal-article","created":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T14:02:55Z","timestamp":1540389775000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Molecular weight of surface immobilized hyaluronic acid influences CD44-mediated binding of gastric cancer cells"],"prefix":"10.1038","volume":"8","author":[{"given":"Sara","family":"Amorim","sequence":"first","affiliation":[]},{"given":"Diana Soares","family":"da Costa","sequence":"additional","affiliation":[]},{"given":"Daniela","family":"Freitas","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0286-6639","authenticated-orcid":false,"given":"Celso A.","family":"Reis","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4295-6129","authenticated-orcid":false,"given":"Rui L.","family":"Reis","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6818-3374","authenticated-orcid":false,"given":"Iva","family":"Pashkuleva","sequence":"additional","affiliation":[]},{"given":"Ricardo A.","family":"Pires","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2018,10,30]]},"reference":[{"key":"34445_CR1","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nrc1391","volume":"4","author":"BP Toole","year":"2004","unstructured":"Toole, B. P. Hyaluronan: From extracellular glue to pericellular cue. Nat Rev Cancer 4, 528\u2013539 (2004).","journal-title":"Nat Rev Cancer"},{"key":"34445_CR2","doi-asserted-by":"crossref","unstructured":"Misra, S., Hascall, V. C., Markwald, R. R. & Ghatak, S. Interactions between hyaluronan and its receptors (CD44, RHAMM) regulate the activities of inflammation and cancer. Front Immunol 6 (2015).","DOI":"10.3389\/fimmu.2015.00201"},{"key":"34445_CR3","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/nrc1649","volume":"5","author":"MM Fuster","year":"2005","unstructured":"Fuster, M. M. & Esko, J. D. The sweet and sour of cancer: Glycans as novel therapeutic targets. Nat Rev Cancer 5, 526\u2013542 (2005).","journal-title":"Nat Rev Cancer"},{"key":"34445_CR4","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/nrc3982","volume":"15","author":"SS Pinho","year":"2015","unstructured":"Pinho, S. S. & Reis, C. A. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer 15, 540\u2013555 (2015).","journal-title":"Nat Rev Cancer"},{"key":"34445_CR5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1046\/j.1365-2567.1998.00431.x","volume":"93","author":"G Borland","year":"1998","unstructured":"Borland, G., Ross, J. A. & Guy, K. Forms and functions of CD44. Immunology 93, 139\u2013148 (1998).","journal-title":"Immunology"},{"key":"34445_CR6","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/S1357-2725(01)00166-2","volume":"34","author":"CM Isacke","year":"2002","unstructured":"Isacke, C. M. & Yarwood, H. The hyaluronan receptor, CD44. Int J Biochem Cell B 34, 718\u2013721 (2002).","journal-title":"Int J Biochem Cell B"},{"key":"34445_CR7","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1136\/mp.52.1.25","volume":"52","author":"HF Hsieh","year":"1999","unstructured":"Hsieh, H. F., Yu, J. C., Lo, L. I., Chiu, S. C. & Harn, H. J. Molecular studies into the role of CD44 variants in metastasis in gastric cancer. J Clin Pathol-Mol Pa 52, 25\u201328 (1999).","journal-title":"J Clin Pathol-Mol Pa"},{"key":"34445_CR8","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1038\/labinvest.2010.155","volume":"90","author":"CB da Cunha","year":"2010","unstructured":"da Cunha, C. B. et al. De novo expression of CD44 variants in sporadic and hereditary gastric cancer. Laboratory investigation; a journal of technical methods and pathology 90, 1604\u20131614 (2010).","journal-title":"Laboratory investigation; a journal of technical methods and pathology"},{"key":"34445_CR9","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s11010-014-2156-6","volume":"396","author":"D Yu","year":"2014","unstructured":"Yu, D., Shin, H. S., Choi, G. & Lee, Y. C. Proteomic analysis of CD44(+) and CD44(\u2212) gastric cancer cells. Mol Cell Biochem 396, 213\u2013220 (2014).","journal-title":"Mol Cell Biochem"},{"key":"34445_CR10","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1002\/stem.30","volume":"27","author":"S Takaishi","year":"2009","unstructured":"Takaishi, S. et al. Identification of Gastric Cancer Stem Cells Using the Cell Surface Marker CD44. Stem Cells 27, 1006\u20131020 (2009).","journal-title":"Stem Cells"},{"key":"34445_CR11","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.canlet.2013.03.035","volume":"338","author":"SR Singh","year":"2013","unstructured":"Singh, S. R. Gastric cancer stem cells: A novel therapeutic target. Cancer Lett 338, 110\u2013119 (2013).","journal-title":"Cancer Lett"},{"key":"34445_CR12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.matbio.2016.10.001","volume":"59","author":"E Karousou","year":"2017","unstructured":"Karousou, E. et al. Roles and targeting of the HAS\/hyaluronan\/CD44 molecular system in cancer. Matrix Biology 59, 3\u201322 (2017).","journal-title":"Matrix Biology"},{"key":"34445_CR13","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.canlet.2016.02.031","volume":"375","author":"T Chanmee","year":"2016","unstructured":"Chanmee, T., Ontong, P. & Itano, N. Hyaluronan: A modulator of the tumor microenvironment. Cancer Lett 375, 20\u201330 (2016).","journal-title":"Cancer Lett"},{"key":"34445_CR14","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.ejcb.2006.05.009","volume":"85","author":"R Stern","year":"2006","unstructured":"Stern, R., Asari, A. A. & Sugahara, K. N. Hyaluronan fragments: An information-rich system. Eur J Cell Biol 85, 699\u2013715 (2006).","journal-title":"Eur J Cell Biol"},{"key":"34445_CR15","doi-asserted-by":"publisher","first-page":"563818","DOI":"10.1155\/2015\/563818","volume":"2015","author":"JM Cyphert","year":"2015","unstructured":"Cyphert, J. M., Trempus, C. S. & Garantziotis, S. Size Matters: Molecular Weight Specificity of Hyaluronan Effects in Cell Biology. Int J Cell Biol 2015, 563818 (2015).","journal-title":"Int J Cell Biol"},{"key":"34445_CR16","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.actbio.2016.12.026","volume":"50","author":"J Sapudom","year":"2017","unstructured":"Sapudom, J. et al. Molecular weight specific impact of soluble and immobilized hyaluronan on CD44 expressing melanoma cells in 3D collagen matrices. Acta Biomater 50, 259\u2013270 (2017).","journal-title":"Acta Biomater"},{"key":"34445_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00432-016-2213-5","volume":"143","author":"RL Wu","year":"2017","unstructured":"Wu, R. L., Huang, L., Zhao, H. C. & Geng, X. P. Hyaluronic acid in digestive cancers. J Cancer Res Clin 143, 1\u201316 (2017).","journal-title":"J Cancer Res Clin"},{"key":"34445_CR18","doi-asserted-by":"publisher","first-page":"9208","DOI":"10.1016\/j.biomaterials.2014.07.033","volume":"35","author":"HJ Yao","year":"2014","unstructured":"Yao, H. J., Zhang, Y. G., Sun, L. & Liu, Y. The effect of hyaluronic acid functionalized carbon nanotubes loaded with salinomycin on gastric cancer stem cells. Biomaterials 35, 9208\u20139223 (2014).","journal-title":"Biomaterials"},{"key":"34445_CR19","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1634\/stemcells.2005-0186","volume":"24","author":"H Zhu","year":"2006","unstructured":"Zhu, H. et al. The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix. Stem Cells 24, 928\u2013935 (2006).","journal-title":"Stem Cells"},{"key":"34445_CR20","doi-asserted-by":"publisher","first-page":"8158","DOI":"10.1016\/j.actbio.2013.05.031","volume":"9","author":"N Altgarde","year":"2013","unstructured":"Altgarde, N. et al. Probing the biofunctionality of biotinylated hyaluronan and chondroitin sulfate by hyaluronidase degradation and aggrecan interaction. Acta Biomater 9, 8158\u20138166 (2013).","journal-title":"Acta Biomater"},{"key":"34445_CR21","doi-asserted-by":"publisher","first-page":"8803","DOI":"10.1039\/c0jm01605e","volume":"20","author":"I Pashkuleva","year":"2010","unstructured":"Pashkuleva, I. & Reis, R. L. Sugars: burden or biomaterials of the future? J Mater Chem 20, 8803\u20138818 (2010).","journal-title":"J Mater Chem"},{"key":"34445_CR22","doi-asserted-by":"publisher","first-page":"10034","DOI":"10.1021\/acsami.5b02479","volume":"7","author":"DS da Costa","year":"2015","unstructured":"da Costa, D. S. et al. Adhesion of Adipose-Derived Mesenchymal Stem Cells to Glycosaminoglycan Surfaces with Different Protein Patterns. Acs Appl Mater Inter 7, 10034\u201310043 (2015).","journal-title":"Acs Appl Mater Inter"},{"key":"34445_CR23","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1002\/adma.200901327","volume":"22","author":"T Boudou","year":"2010","unstructured":"Boudou, T., Crouzier, T., Ren, K. F., Blin, G. & Picart, C. Multiple Functionalities of Polyelectrolyte Multilayer Films: New Biomedical Applications. Adv Mater 22, 441\u2013467 (2010).","journal-title":"Adv Mater"},{"key":"34445_CR24","doi-asserted-by":"publisher","first-page":"8883","DOI":"10.1021\/cr400531v","volume":"114","author":"J Borges","year":"2014","unstructured":"Borges, J. & Mano, J. F. Molecular Interactions Driving the Layer-by-Layer Assembly of Multilayers. Chem Rev 114, 8883\u20138942 (2014).","journal-title":"Chem Rev"},{"key":"34445_CR25","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/j.colsurfb.2016.05.069","volume":"145","author":"R Teixeira","year":"2016","unstructured":"Teixeira, R., Reis, R. L. & Pashkuleva, I. Influence of the sulfation degree of glycosaminoglycans on their multilayer assembly with poly-L-lysine. Colloid Surface B 145, 567\u2013575 (2016).","journal-title":"Colloid Surface B"},{"key":"34445_CR26","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1021\/bm8012378","volume":"10","author":"T Crouzier","year":"2009","unstructured":"Crouzier, T. & Picart, C. Ion Pairing and Hydration in Polyelectrolyte Multilayer Films Containing Polysaccharides. Biomacromolecules 10, 433\u2013442 (2009).","journal-title":"Biomacromolecules"},{"key":"34445_CR27","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1021\/la062728k","volume":"23","author":"C Porcel","year":"2007","unstructured":"Porcel, C. et al. Influence of the polyelectrolyte molecular weight on exponentially growing multilayer films in the linear regime. Langmuir 23, 1898\u20131904 (2007).","journal-title":"Langmuir"},{"key":"34445_CR28","doi-asserted-by":"publisher","first-page":"6939","DOI":"10.1039\/C4TB01071J","volume":"2","author":"S Amorim","year":"2014","unstructured":"Amorim, S., Martins, A., Neves, N. M., Reis, R. L. & Pires, R. A. Hyaluronic acid\/poly-L-lysine bilayered silica nanoparticles enhance the osteogenic differentiation of human mesenchymal stem cells. J Mater Chem B 2, 6939\u20136946 (2014).","journal-title":"J Mater Chem B"},{"key":"34445_CR29","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1021\/bm200070k","volume":"12","author":"LY Shen","year":"2011","unstructured":"Shen, L. Y., Chaudouet, P., Ji, J. A. & Picart, C. pH-Amplified Multilayer Films Based on Hyaluronan: Influence of HA Molecular Weight and Concentration on Film Growth and Stability. Biomacromolecules 12, 1322\u20131331 (2011).","journal-title":"Biomacromolecules"},{"key":"34445_CR30","doi-asserted-by":"publisher","first-page":"7414","DOI":"10.1021\/la010848g","volume":"17","author":"C Picart","year":"2001","unstructured":"Picart, C. et al. Buildup mechanism for poly(L-lysine)\/hyaluronic acid films onto a solid surface. Langmuir 17, 7414\u20137424 (2001).","journal-title":"Langmuir"},{"key":"34445_CR31","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1238\/Physica.Regular.059a00391","volume":"59","author":"MV Voinova","year":"1999","unstructured":"Voinova, M. V., Rodahl, M., Jonson, M. & Kasemo, B. Viscoelastic acoustic response of layered polymer films at fluid-solid interfaces: Continuum mechanics approach. Phys Scripta 59, 391\u2013396 (1999).","journal-title":"Phys Scripta"},{"key":"34445_CR32","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1021\/bm200258q","volume":"12","author":"S Grohmann","year":"2011","unstructured":"Grohmann, S., Rothe, H., Frant, M. & Liefeith, K. Colloidal force spectroscopy and cell biological investigations on biomimetic polyelectrolyte multilayer coatings composed of chondroitin sulfate and heparin. Biomacromolecules 12, 1987\u20131997 (2011).","journal-title":"Biomacromolecules"},{"key":"34445_CR33","doi-asserted-by":"publisher","first-page":"9224","DOI":"10.1021\/ja044385n","volume":"127","author":"P Kujawa","year":"2005","unstructured":"Kujawa, P., Moraille, P., Sanchez, J., Badia, A. & Winnik, F. M. Effect of molecular weight on the exponential growth and morphology of hyaluronan\/chitosan multilayers: A surface plasmon resonance spectroscopy and atomic force microscopy investigation. J Am Chem Soc 127, 9224\u20139234 (2005).","journal-title":"J Am Chem Soc"},{"key":"34445_CR34","doi-asserted-by":"publisher","first-page":"43094","DOI":"10.1074\/jbc.M112.349209","volume":"287","author":"CX Yang","year":"2012","unstructured":"Yang, C. X. et al. The High and Low Molecular Weight Forms of Hyaluronan Have Distinct Effects on CD44 Clustering. J Biol Chem 287, 43094\u201343107 (2012).","journal-title":"J Biol Chem"},{"key":"34445_CR35","doi-asserted-by":"publisher","first-page":"30170","DOI":"10.1074\/jbc.M110.137562","volume":"285","author":"PM Wolny","year":"2010","unstructured":"Wolny, P. M. et al. Analysis of CD44-Hyaluronan Interactions in an Artificial Membrane System: Insights Into The Distinct Binding Properties Of High And Low Molecular Weight Hyaluronan. J Biol Chem 285, 30170\u201330180 (2010).","journal-title":"J Biol Chem"},{"key":"34445_CR36","doi-asserted-by":"publisher","first-page":"12271","DOI":"10.1073\/pnas.95.21.12271","volume":"95","author":"F Hook","year":"1998","unstructured":"Hook, F., Rodahl, M., Kasemo, B. & Brzezinski, P. Structural changes in hemoglobin during adsorption to solid surfaces: Effects of pH, ionic strength, and ligand binding. PNAS 95, 12271\u201312276 (1998).","journal-title":"PNAS"},{"key":"34445_CR37","doi-asserted-by":"publisher","first-page":"7983","DOI":"10.1021\/la400871c","volume":"29","author":"S Amorim","year":"2013","unstructured":"Amorim, S., Pires, R. A., da Costa, D. S., Reis, R. L. & Pashkuleva, I. Interactions between Exogenous FGF-2 and Sulfonic Groups: in Situ Characterization and Impact on the Morphology of Human Adipose-Derived Stem Cells. Langmuir 29, 7983\u20137992 (2013).","journal-title":"Langmuir"},{"key":"34445_CR38","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1159\/000452570","volume":"40","author":"M Fang","year":"2016","unstructured":"Fang, M. et al. CD44 and CD44v6 are Correlated with Gastric Cancer Progression and Poor Patient Prognosis: Evidence from 42 Studies. Cell Physiol Biochem 40, 567\u2013578 (2016).","journal-title":"Cell Physiol Biochem"},{"key":"34445_CR39","doi-asserted-by":"crossref","unstructured":"Rios de la Rosa Julio, M., Tirella, A. & Tirelli, N. Receptor\u2010Targeted Drug Delivery and the (Many) Problems We Know of: The Case of CD44 and Hyaluronic Acid. Advanced Biosystems 0, 1800049.","DOI":"10.1002\/adbi.201800049"},{"key":"34445_CR40","doi-asserted-by":"publisher","first-page":"397","DOI":"10.5009\/gnl.2011.5.4.397","volume":"5","author":"BI Jang","year":"2011","unstructured":"Jang, B. I., Li, Y., Graham, D. Y. & Cen, P. T. The Role of CD44 in the Pathogenesis, Diagnosis, and Therapy of Gastric Cancer. Gut Liver 5, 397\u2013405 (2011).","journal-title":"Gut Liver"},{"key":"34445_CR41","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1097\/00022744-200106000-00006","volume":"9","author":"Y Xin","year":"2001","unstructured":"Xin, Y. et al. CD44V6 in gastric carcinoma: A marker of tumor progression. Appl Immunohisto M M 9, 138\u2013142 (2001).","journal-title":"Appl Immunohisto M M"},{"key":"34445_CR42","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1002\/jso.10082","volume":"79","author":"A Yamaguchi","year":"2002","unstructured":"Yamaguchi, A. et al. Expression of CD44v6 in advanced gastric cancer and its relationship to hematogenous metastasis and long-term prognosis. J Surg Oncol 79, 230\u2013235 (2002).","journal-title":"J Surg Oncol"},{"key":"34445_CR43","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1074\/mcp.M114.046862","volume":"14","author":"D Campos","year":"2015","unstructured":"Campos, D. et al. Probing the O-Glycoproteome of Gastric Cancer Cell Lines for Biomarker Discovery. Mol Cell Proteomics 14, 1616\u20131629 (2015).","journal-title":"Mol Cell Proteomics"},{"key":"34445_CR44","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1111\/jocd.12009","volume":"11","author":"HR Choi","year":"2012","unstructured":"Choi, H. R. et al. Oligosaccharides of hyaluronic acid increased epidermal cell stemness by modulation of integrin expression. J Cosmet Dermatol-Us 11, 290\u2013296 (2012).","journal-title":"J Cosmet Dermatol-Us"},{"key":"34445_CR45","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.biomaterials.2013.09.066","volume":"35","author":"A Chopra","year":"2014","unstructured":"Chopra, A. et al. Augmentation of integrin-mediated mechanotransduction by hyaluronic acid. Biomaterials 35, 71\u201382 (2014).","journal-title":"Biomaterials"},{"key":"34445_CR46","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1083\/jcb.132.6.1199","volume":"132","author":"A Bartolazzi","year":"1996","unstructured":"Bartolazzi, A., Nocks, A., Aruffo, A., Spring, F. & Stamenkovic, I. Glycosylation of CD44 is implicated in CD44-mediated cell adhesion to hyaluronan. The Journal of Cell Biology 132, 1199\u20131208 (1996).","journal-title":"The Journal of Cell Biology"},{"key":"34445_CR47","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s10585-006-9014-1","volume":"23","author":"AM Weaver","year":"2006","unstructured":"Weaver, A. M. Invadopodia: specialized cell structures for cancer invasion. Clin Exp Metastas 23, 97\u2013105 (2006).","journal-title":"Clin Exp Metastas"},{"key":"34445_CR48","doi-asserted-by":"publisher","first-page":"273","DOI":"10.4161\/cam.28349","volume":"8","author":"A Bergman","year":"2014","unstructured":"Bergman, A., Condeelis, J. S. & Gligorijevic, B. Invadopodia in context. Cell Adhes Migr 8, 273\u2013279 (2014).","journal-title":"Cell Adhes Migr"},{"key":"34445_CR49","doi-asserted-by":"publisher","first-page":"226","DOI":"10.4161\/cam.28346","volume":"8","author":"CM Gould","year":"2014","unstructured":"Gould, C. M. & Courtneidge, S. A. Regulation of invadopodia by the tumor microenvironment. Cell Adhes Migr 8, 226\u2013235 (2014).","journal-title":"Cell Adhes Migr"},{"key":"34445_CR50","first-page":"642","volume":"1773","author":"H Yamaguchi","year":"2007","unstructured":"Yamaguchi, H. & Condeelis, J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Bba-Mol Cell Res 1773, 642\u2013652 (2007).","journal-title":"Bba-Mol Cell Res"},{"key":"34445_CR51","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1242\/jcs.093781","volume":"125","author":"SM MacGrath","year":"2012","unstructured":"MacGrath, S. M. & Koleske, A. J. Cortactin in cell migration and cancer at a glance. J Cell Sci 125, 1621\u20131626 (2012).","journal-title":"J Cell Sci"},{"key":"34445_CR52","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.ejcb.2007.01.003","volume":"86","author":"BA Webb","year":"2007","unstructured":"Webb, B. A., Jia, L., Eves, R. & Mak, A. S. Dissecting the functional domain requirements of cortactin in invadopodia formation. Eur J Cell Biol 86, 189\u2013206 (2007).","journal-title":"Eur J Cell Biol"},{"key":"34445_CR53","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.tcb.2017.03.003","volume":"27","author":"RJ Eddy","year":"2017","unstructured":"Eddy, R. J., Weidmann, M. D., Sharma, V. P. & Condeelis, J. S. Tumor Cell Invadopodia: Invasive Protrusions that Orchestrate Metastasis. Trends Cell Biol 27, 595\u2013607 (2017).","journal-title":"Trends Cell Biol"},{"key":"34445_CR54","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1083\/jcb.200309034","volume":"164","author":"FM Helwani","year":"2004","unstructured":"Helwani, F. M. et al. Cortactin is necessary for E-cadherin\u2013mediated contact formation and actin reorganization. The Journal of Cell Biology 164, 899\u2013910 (2004).","journal-title":"The Journal of Cell Biology"},{"key":"34445_CR55","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/nrm3141","volume":"12","author":"DA Murphy","year":"2011","unstructured":"Murphy, D. A. & Courtneidge, S. A. The \u2018ins\u2019 and \u2018outs\u2019 of podosomes and invadopodia: characteristics, formation and function. Nat Rev Mol Cell Bio 12, 413\u2013426 (2011).","journal-title":"Nat Rev Mol Cell Bio"},{"key":"34445_CR56","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1083\/jcb.200812176","volume":"186","author":"M Oser","year":"2009","unstructured":"Oser, M. et al. Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. J Cell Biol 186, 571\u2013587 (2009).","journal-title":"J Cell Biol"},{"key":"34445_CR57","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/j.cub.2008.07.090","volume":"18","author":"NR Alexander","year":"2008","unstructured":"Alexander, N. R. et al. Extracellular matrix rigidity promotes invadopodia activity. Curr Biol 18, 1295\u20131299 (2008).","journal-title":"Curr Biol"},{"key":"34445_CR58","doi-asserted-by":"crossref","unstructured":"Chellaiah, M. A. CD44-Src signaling promotes invadopodia formation in prostate cancer (PC3) cells. OA Cancer 1 (2013).","DOI":"10.13172\/2053-3918-1-2-985"},{"key":"34445_CR59","doi-asserted-by":"crossref","unstructured":"Chen, J. W. E. et al. Influence of Hyaluronic Acid Transitions in Tumor Microenvironment on Glioblastoma Malignancy and Invasive Behavior. Front Mater 5 (2018).","DOI":"10.3389\/fmats.2018.00039"},{"key":"34445_CR60","doi-asserted-by":"crossref","unstructured":"Minsky, B. B., Antoni, C. H. & Boehm, H. Controlled Immobilization Strategies to Probe Short Hyaluronan-Protein Interactions. Sci Rep-Uk 6 (2016).","DOI":"10.1038\/srep21608"},{"key":"34445_CR61","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.3727\/096368917X694831","volume":"26","author":"K Tsuji","year":"2017","unstructured":"Tsuji, K. et al. Effects of Different Cell-Detaching Methods on the Viability and Cell Surface Antigen Expression of Synovial Mesenchymal Stem Cells. Cell Transplantation 26, 1089\u20131102 (2017).","journal-title":"Cell Transplantation"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34445-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34445-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34445-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T10:57:39Z","timestamp":1671620259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34445-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,30]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["34445"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-34445-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,30]]},"assertion":[{"value":"16 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"16058"}}