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The broadly expressed secreted protein stanniocalcin 2 (STC2), also implicated in tumor inflammation, is an HRG interaction partner. With the aim to biochemically characterize the HRG and STC2 complex, binding of recombinant HRG and STC2 preparations to each other and to cells was explored using the quartz crystal microbalance (QCM) methodology. The functionality of recombinant proteins was tested in a phagocytosis assay, where HRG increased phagocytosis by monocytic U937 cells while STC2 suppressed HRG-induced phagocytosis. The binding of HRG to STC2, measured using QCM, showed an affinity between the proteins in the nanomolar range, and both HRG and STC2 bound individually and in combination to vitamin D3-treated, differentiated U937 monocytes. HRG, but not STC2, also bound to formaldehyde-fixed U937 cells irrespective of their differentiation stage in part through the interaction with heparan sulfate. These data show that HRG and STC2 bind to each other as well as to U937 monocytes with high affinity, supporting the relevance of these interactions in monocyte\/macrophage polarity.<\/jats:p>","DOI":"10.3390\/cells11172684","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T21:01:31Z","timestamp":1661806891000},"page":"2684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Quartz Crystal Microbalance Measurement of Histidine-Rich Glycoprotein and Stanniocalcin-2 Binding to Each Other and to Inflammatory Cells"],"prefix":"10.3390","volume":"11","author":[{"given":"Tor","family":"Persson Skare","sequence":"first","affiliation":[{"name":"Science for Life and Beijer Laboratories, Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskj\u00f6ldsv 20, 751 85 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kaito","sequence":"additional","affiliation":[{"name":"Science for Life and Beijer Laboratories, Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskj\u00f6ldsv 20, 751 85 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Durall","sequence":"additional","affiliation":[{"name":"Attana AB, Greta Arwidssons V\u00e4g 21, 114 19 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodor","family":"Aastrup","sequence":"additional","affiliation":[{"name":"Attana AB, Greta Arwidssons V\u00e4g 21, 114 19 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Claesson-Welsh","sequence":"additional","affiliation":[{"name":"Science for Life and Beijer Laboratories, Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskj\u00f6ldsv 20, 751 85 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ccr.2010.11.009","article-title":"HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF","volume":"19","author":"Rolny","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_2","unstructured":"Jeon, K.W. (2013). Chapter Nine\u2014New Insights into the Functions of Histidine-Rich Glycoprotein. International Review of Cell and Molecular Biology, Academic Press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1182\/blood-2010-09-303842","article-title":"Histidine-rich glycoprotein: The Swiss Army knife of mammalian plasma","volume":"117","author":"Poon","year":"2011","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1182\/blood-2010-02-271858","article-title":"Histidine-rich glycoprotein promotes bacterial entrapment in clots and decreases mortality in a mouse model of sepsis","volume":"116","author":"Shannon","year":"2010","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6653","DOI":"10.1021\/bi962573n","article-title":"Histidine-Rich Glycoprotein Binds to Human IgG and C1q and Inhibits the Formation of Insoluble Immune Complexes","volume":"36","author":"Gorgani","year":"1997","journal-title":"Biochemistry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10298","DOI":"10.1074\/jbc.M508483200","article-title":"The anti-angiogenic His\/Pro-rich fragment of histidine-rich glycoprotein binds to endothelial cell heparan sulfate in a Zn2+-dependent manner","volume":"281","author":"Vanwildemeersch","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1158\/0008-5472.CAN-03-1941","article-title":"A fragment of histidine-rich glycoprotein is a potent inhibitor of tumor vascularization","volume":"64","author":"Olsson","year":"2004","journal-title":"Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1182\/blood-2013-11-535963","article-title":"Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: Implications for angiogenic regulation","volume":"123","author":"Kassaar","year":"2014","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0968-0004(02)02169-2","article-title":"Intrinsically unstructured proteins","volume":"27","author":"Tompa","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s12016-007-8058-6","article-title":"Histidine-rich glycoprotein modulation of immune\/autoimmune, vascular, and coagulation systems","volume":"34","author":"Blank","year":"2008","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.matbio.2015.06.002","article-title":"Histidine-rich glycoprotein blocks collagen-binding integrins and adhesion of endothelial cells through low-affinity interaction with alpha2 integrin","volume":"48","author":"Roche","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10223","DOI":"10.1038\/s41598-021-89555-z","article-title":"Histidine-rich glycoprotein as a prognostic biomarker for sepsis","volume":"11","author":"Kuroda","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1111\/j.1538-7836.2005.01238.x","article-title":"Enhanced blood coagulation and fibrinolysis in mice lacking histidine-rich glycoprotein (HRG)","volume":"3","author":"Ensslen","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.2741\/3422","article-title":"Type 3 cystatins; fetuins, kininogen and histidine-rich glycoprotein","volume":"14","author":"Lee","year":"2009","journal-title":"Front. Biosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1158\/0008-5472.CAN-11-2194","article-title":"Genetic deficiency in plasma protein HRG enhances tumor growth and metastasis by exacerbating immune escape and vessel abnormalization","volume":"72","author":"Tugues","year":"2012","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1158\/1535-7163.MCT-18-0097","article-title":"Leukocyte Differentiation by Histidine-Rich Glycoprotein\/Stanniocalcin-2 Complex Regulates Murine Glioma Growth through Modulation of Antitumor Immunity","volume":"17","author":"Roche","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Fagerberg","year":"2015","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3389\/fendo.2020.00172","article-title":"New Insights Into Physiological and Pathophysiological Functions of Stanniocalcin 2","volume":"11","author":"Joshi","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.mce.2011.11.007","article-title":"Evolution and roles of stanniocalcin","volume":"349","author":"Yeung","year":"2012","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1210\/en.2007-1219","article-title":"The murine stanniocalcin 2 gene is a negative regulator of postnatal growth","volume":"149","author":"Chang","year":"2008","journal-title":"Endocrinology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5474","DOI":"10.1039\/C7NR07887K","article-title":"Label-free in-flow detection of receptor recognition motifs on the biomolecular corona of nanoparticles","volume":"10","author":"Gianneli","year":"2018","journal-title":"Nanoscale"},{"key":"ref_22","first-page":"5862","article-title":"Induction of differentiation of the human histiocytic lymphoma cell line U-937 by 1 alpha,25-dihydroxycholecalciferol","volume":"43","author":"Olsson","year":"1983","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/ijc.2910170504","article-title":"Establishment and characterization of a human histiocytic lymphoma cell line (U-937)","volume":"17","author":"Nilsson","year":"1976","journal-title":"Int. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tugues, S., Roche, F., Noguer, O., Orlova, A., Bhoi, S., Padhan, N., \u00c5kerud, P., Honjo, S., Selvaraju, R.K., and Mazzone, M. (2014). Histidine-rich glycoprotein uptake and turnover is mediated by mononuclear phagocytes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107483"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rockberg, J., and Nilvebrant, J. (2018). Label-Free Cell-Based Assay for Characterization of Biomolecules and Receptors. Epitope Mapping Protocols, Springer.","DOI":"10.1007\/978-1-4939-7841-0"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5366","DOI":"10.1021\/acs.analchem.8b00504","article-title":"Reliable Strategy for Analysis of Complex Biosensor Data","volume":"90","author":"Multia","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jconrel.2018.05.002","article-title":"Histidine-rich glycoprotein-induced vascular normalization improves EPR-mediated drug targeting to and into tumors","volume":"282","author":"Theek","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1021\/bm020116i","article-title":"Quartz Crystal Microbalance:\u2009 A Useful Tool for Studying Thin Polymer Films and Complex Biomolecular Systems at the Solution\u2212Surface Interface","volume":"4","author":"Marx","year":"2003","journal-title":"Biomacromolecules"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.bios.2012.02.047","article-title":"Real-time analysis of the carbohydrates on cell surfaces using a QCM biosensor: A lectin-based approach","volume":"35","author":"Pei","year":"2012","journal-title":"Biosens. Bioelectron."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1369\/jhc.2009.954321","article-title":"The impact of tissue fixatives on morphology and antibody-based protein profiling in tissues and cells","volume":"58","author":"Paavilainen","year":"2010","journal-title":"J. Histochem. Cytochem."},{"key":"ref_31","first-page":"329","article-title":"Induction of CD14 Expression and Differentiation to Monocytes or Mature Macrophages in Promyelocytic Cell Lines: New Approach","volume":"3","author":"Zamani","year":"2013","journal-title":"Adv. Pharm. Bull."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/17\/2684\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:19:26Z","timestamp":1760141966000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/17\/2684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,29]]},"references-count":31,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["cells11172684"],"URL":"https:\/\/doi.org\/10.3390\/cells11172684","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,29]]}}}