{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:29:06Z","timestamp":1790296146888,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004271","name":"Ateneo project-Avvio alla Ricerca","doi-asserted-by":"publisher","award":["AR22117A583BC114"],"award-info":[{"award-number":["AR22117A583BC114"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gliomas are the most common primary malignant brain tumors. Glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4) is the most aggressive form of glioma and is characterized by extensive hypoxic areas that strongly correlate with tumor malignancy. Hypoxia promotes several processes, including stemness, migration, invasion, angiogenesis, and radio- and chemoresistance, that have direct impacts on treatment failure. Thus, there is still an increasing need to identify novel targets to limit GBM relapse. Polysialic acid (PSA) is a carbohydrate composed of a linear polymer of \u03b12,8-linked sialic acids, primarily attached to the Neural Cell Adhesion Molecule (NCAM). It is considered an oncodevelopmental antigen that is re-expressed in various tumors. High levels of PSA-NCAM are associated with high-grade and poorly differentiated tumors. Here, we investigated the effect of PSA inhibition in GBM cells under low oxygen concentrations. Our main results highlight the way in which hypoxia stimulates polysialylation in U87-MG cells and in a GBM primary culture. By lowering PSA levels with the sialic acid analog, F-NANA, we also inhibited GBM cell migration and interfered with their differentiation influenced by the hypoxic microenvironment. Our findings suggest that PSA may represent a possible molecular target for the development of alternative pharmacological strategies to manage a devastating tumor like GBM.<\/jats:p>","DOI":"10.3390\/ijms23179563","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T21:03:51Z","timestamp":1661375031000},"page":"9563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Polysialic Acid Sustains the Hypoxia-Induced Migration and Undifferentiated State of Human Glioblastoma Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8468-0677","authenticated-orcid":false,"given":"Paolo","family":"Rosa","sequence":"first","affiliation":[{"name":"Department of Medical-Surgical Sciences and Biotechnologies, University of Rome \u201cSapienza\u201d, Polo Pontino, C.so della Repubblica 79, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Scibetta","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Biotechnologies, University of Rome \u201cSapienza\u201d, Polo Pontino, C.so della Repubblica 79, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pepe","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Via Dell\u2019Elettronica, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8950-9780","authenticated-orcid":false,"given":"Giorgio","family":"Mangino","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Biotechnologies, University of Rome \u201cSapienza\u201d, Polo Pontino, C.so della Repubblica 79, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Capocci","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Via Dell\u2019Elettronica, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5507-3811","authenticated-orcid":false,"given":"Sam J.","family":"Moons","sequence":"additional","affiliation":[{"name":"Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Boltje","sequence":"additional","affiliation":[{"name":"Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-7912","authenticated-orcid":false,"given":"Francesco","family":"Fazi","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, University of Rome \u201cSapienza\u201d, Via A. Scarpa, 14-16, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9837-8690","authenticated-orcid":false,"given":"Vincenzo","family":"Petrozza","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Biotechnologies, University of Rome \u201cSapienza\u201d, Polo Pontino, C.so della Repubblica 79, 04100 Latina, Italy"},{"name":"ICOT, Istituto Chirurgico Ortopedico Traumatologico, Via F. Faggiana 1668, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Di Pardo","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Via Dell\u2019Elettronica, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Maglione","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Via Dell\u2019Elettronica, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Calogero","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Biotechnologies, University of Rome \u201cSapienza\u201d, Polo Pontino, C.so della Repubblica 79, 04100 Latina, Italy"},{"name":"ICOT, Istituto Chirurgico Ortopedico Traumatologico, Via F. Faggiana 1668, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6242","DOI":"10.1073\/pnas.97.12.6242","article-title":"Glioblastoma multiforme: The terminator","volume":"97","author":"Holland","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10014-010-0011-3","article-title":"Glioma-initiating cells and molecular pathology: Implications for therapy","volume":"28","author":"Natsume","year":"2011","journal-title":"Brain Tumor Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/sj.onc.1209785","article-title":"Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine","volume":"26","author":"Roos","year":"2007","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/sj.cdd.4401359","article-title":"Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells","volume":"11","author":"Kanzawa","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_6","first-page":"1957","article-title":"p53 effects both the duration of G2\/M arrest and the fate of temozolomide-treated human glioblastoma cells","volume":"61","author":"Hirose","year":"2001","journal-title":"Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1158\/1078-0432.CCR-07-1719","article-title":"Mechanisms of chemoresistance to alkylating agents in malignant glioma","volume":"14","author":"Sarkaria","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6866","DOI":"10.1002\/jcp.26448","article-title":"BK channels blockage inhibits hypoxia-induced migration and chemoresistance to cisplatin in human glioblastoma cells","volume":"233","author":"Rosa","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"399","DOI":"10.7150\/ijms.5407","article-title":"Hypoxia Enhances Stemness of Cancer Stem Cells in Glioblastoma: An In Vitro Study","volume":"10","author":"Li","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1016\/j.bbagen.2017.07.001","article-title":"A synthetic BMP-2 mimicking peptide induces glioblastoma stem cell differentiation","volume":"1861","author":"Rampazzo","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1158\/1078-0432.CCR-09-1800","article-title":"Differentiation therapy exerts antitumor effects on stem-like glioma cells","volume":"16","author":"Campos","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"925","DOI":"10.2174\/156800912803251225","article-title":"Polysialyltransferase: A New Target in Metastatic Cancer","volume":"12","author":"Falconer","year":"2012","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1093\/glycob\/cwn084","article-title":"Direct binding of polysialic acid to a brain-derived neurotrophic factor depends on the degree of polymerization","volume":"18","author":"Kanato","year":"2008","journal-title":"Glycobiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/0896-6273(94)90028-0","article-title":"N-CAM mutation inhibits tangential neuronal migration and is phenocopied by enzymatic removal of polysialic acid","volume":"13","author":"Ono","year":"1994","journal-title":"Neuron"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9372","DOI":"10.1523\/JNEUROSCI.1702-04.2004","article-title":"Polysialylated neural cell adhesion molecule promotes remodeling and formation of hippocampal synapses","volume":"24","author":"Dityatev","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bonfanti, L., and Seki, T. (2021). The PSA-NCAM-Positive \u201cImmature\u201d Neurons: An Old Discovery Providing New Vistas on Brain Structural Plasticity. Cells, 10.","DOI":"10.3390\/cells10102542"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0896-6273(90)90310-C","article-title":"Neurite outgrowth in response to transfected N-CAM changes during development and is modulated by polysialic acid","volume":"5","author":"Doherty","year":"1990","journal-title":"Neuron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1093\/brain\/awp117","article-title":"Imbalance of neural cell adhesion molecule and polysialyltransferase alleles causes defective brain connectivity","volume":"132","author":"Hildebrandt","year":"2009","journal-title":"Brain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3109\/10409238.2014.976606","article-title":"Polysialic acid: Biosynthesis, novel functions and applications","volume":"49","author":"Colley","year":"2014","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1021\/nn5061964","article-title":"Targeted delivery of a sialic acid-blocking glycomimetic to cancer cells inhibits metastatic spread","volume":"9","author":"Boltje","year":"2015","journal-title":"ACS Nano"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1021\/acs.jmedchem.8b01757","article-title":"Potent Metabolic Sialylation Inhibitors Based on C-5-Modified Fluorinated Sialic Acids","volume":"62","author":"Heise","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1158\/1535-7163.MCT-13-0279","article-title":"Targeting aberrant sialylation in cancer cells using a fluorinated sialic acid analog impairs adhesion, migration, and in vivo tumor growth","volume":"12","author":"Boltje","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/icb.2016.105","article-title":"Metabolic sialic acid blockade lowers the activation threshold of moDCs for TLR stimulation","volume":"95","author":"Heise","year":"2017","journal-title":"Immunol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1021\/acschembio.1c00868","article-title":"Structure\u2014Activity Relationship of Metabolic Sialic Acid Inhibitors and Labeling Reagents","volume":"17","author":"Moons","year":"2022","journal-title":"ACS Chem. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.1074\/jbc.RA118.002763","article-title":"Combined sialic acid and histone deacetylase (HDAC) inhibitor treatment up-regulates the neuroblastoma antigen GD2","volume":"294","author":"Kroesen","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Amoureux, M.C., Coulibaly, B., Chinot, O., Loundou, A., Metellus, P., Rougon, G., and Figarella-Branger, D. (2010). Polysialic acid neural cell adhesion molecule (psa-ncam) is an adverse prognosis factor in glioblastoma, and regulates olig2 expression in glioma cell lines. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-91"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/sj.onc.1204176","article-title":"A nude mice model of human rhabdomyosarcoma lung metastases for evaluating the role of polysialic acids in the metastatic process","volume":"20","author":"Daniel","year":"2001","journal-title":"Oncogene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1097\/WNR.0000000000001156","article-title":"Hypoxia enhances the migration and invasion of human glioblastoma U87 cells through PI3K\/Akt\/mTOR\/HIF-1\u03b1 pathway","volume":"29","author":"Huang","year":"2018","journal-title":"Neuroreport"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1615\/CritRevEukaryotGeneExpr.2015015601","article-title":"Hypoxia Is the Driving Force Behind GBM and Could Be a New Tool in GBM Treatment","volume":"25","author":"Kalkan","year":"2015","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/neuonc\/now258","article-title":"Hypoxia in the glioblastoma microenvironment: Shaping the phenotype of cancer stem-like cells","volume":"19","author":"Colwell","year":"2017","journal-title":"Neuro-Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6659","DOI":"10.1128\/MCB.00205-07","article-title":"Polysialic Acid-Directed Migration and Differentiation of Neural Precursors Are Essential for Mouse Brain Development","volume":"27","author":"Angata","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0076-6879(10)79002-9","article-title":"Roles of polysialic acid in Migration and differentiation of neural stem cells","volume":"Volume 479","author":"Angata","year":"2010","journal-title":"Methods in Enzymology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/glycob\/cwi071","article-title":"Polysialic acid facilitates tumor invasion by glioma cells","volume":"15","author":"Suzuki","year":"2005","journal-title":"Glycobiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/stem.415","article-title":"Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma","volume":"28","author":"Pistollato","year":"2010","journal-title":"Stem Cells"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Forte, E., Chimenti, I., Rosa, P., Angelini, F., Pagano, F., Calogero, A., Giacomello, A., and Messina, E. (2017). EMT\/MET at the crossroad of stemness, regeneration and oncogenesis: The Ying-Yang equilibrium recapitulated in cell spheroids. Cancers, 9.","DOI":"10.3390\/cancers9080098"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5619472","DOI":"10.1155\/2017\/5619472","article-title":"Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment","volume":"2017","author":"Aponte","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/128_2013_446","article-title":"Polysialic Acid in Brain Development and Synaptic Plasticity","volume":"366","author":"Hildebrandt","year":"2015","journal-title":"Top. Curr. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0896-6273(00)80094-X","article-title":"The role of polysialic acid in migration of olfactory bulb interneuron precursors in the subventricular zone","volume":"16","author":"Hu","year":"1996","journal-title":"Neuron"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3892\/ijmm.2015.2395","article-title":"Enhanced expression of polysialic acid correlates with malignant phenotype in breast cancer cell lines and clinical tissue samples","volume":"37","author":"Wang","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"33026","DOI":"10.1038\/srep33026","article-title":"Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment","volume":"6","author":"Elkashef","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Blaheta, R.A., Daher, F.H., Michaelis, M., Hasenberg, C., Weich, E.M., Jonas, D., Kotchetkov, R., Doerr, H.W., and Cinatl, J. (2006). Chemoresistance induces enhanced adhesion and transendothelial penetration of neuroblastoma cells by down-regulating NCAM surface expression. BMC Cancer, 6.","DOI":"10.1186\/1471-2407-6-294"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.canlet.2015.01.010","article-title":"Hypoxia enhances migration and invasion in glioblastoma by promoting a mesenchymal shift mediated by the HIF1\u03b1\u2014ZEB1 axis","volume":"359","author":"Joseph","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1016\/j.apsb.2021.01.012","article-title":"The reversed intra- and extracellular pH in tumors as a unified strategy to chemotherapeutic delivery using targeted nanocarriers","volume":"11","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S1476-5586(03)80005-2","article-title":"Contributions of Cell Metabolism and H+ Diffusion to the Acidic pH of Tumors","volume":"5","author":"Schomack","year":"2003","journal-title":"Neoplasia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"534","DOI":"10.3389\/fendo.2021.657953","article-title":"Neural Cell Adhesion Molecule Regulates Osteoblastic Differentiation Through Wnt\/\u03b2-Catenin and PI3K-Akt Signaling Pathways in MC3T3-E1 Cells","volume":"12","author":"Cheng","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s41416-020-01126-7","article-title":"Insights into the role of sialylation in cancer progression and metastasis","volume":"124","author":"Dobie","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1007\/s11064-013-0980-9","article-title":"Physiological Role of \u03b2-Catenin\/TCF Signaling in Neurons of the Adult Brain","volume":"38","author":"Wisniewska","year":"2013","journal-title":"Neurochem. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.conb.2008.07.015","article-title":"L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth","volume":"18","author":"Schmid","year":"2008","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1038\/cdd.2008.72","article-title":"Mesenchymal differentiation of glioblastoma stem cells","volume":"15","author":"Pallini","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Pietrobono, S., and Stecca, B. (2021). Aberrant Sialylation in Cancer: Biomarker and Potential Target for Therapeutic Intervention?. Cancers, 13.","DOI":"10.3390\/cancers13092014"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5220","DOI":"10.1111\/febs.13062","article-title":"Hypoxia-inducible factor-2\u03b1 (HIF-2\u03b1), but not HIF-1\u03b1, is essential for hypoxic induction of class III \u03b2-tubulin expression in human glioblastoma cells","volume":"281","author":"Bordji","year":"2014","journal-title":"FEBS J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1016\/j.celrep.2019.07.071","article-title":"Driving Neuronal Differentiation through Reversal of an ERK1\/2-miR-124-SOX9 Axis Abrogates Glioblastoma Aggressiveness","volume":"28","author":"Petri","year":"2019","journal-title":"Cell Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1158\/1541-7786.MCR-06-0005","article-title":"Primary Glioblastomas Express Mesenchymal Stem-Like Properties","volume":"4","author":"Tso","year":"2006","journal-title":"Mol. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1007\/s00018-020-03601-z","article-title":"Polysialic acid and Siglec-E orchestrate negative feedback regulation of microglia activation","volume":"78","author":"Thiesler","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Longhitano, L., Vicario, N., Forte, S., Giallongo, C., Broggi, G., Caltabiano, R., Barbagallo, G.M.V., Altieri, R., Raciti, G., and Di Rosa, M. (2022). Lactate modulates microglia polarization via IGFBP6 expression and remodels tumor microenvironment in glioblastoma. Cancer Immunol. Immunother.","DOI":"10.1007\/s00262-022-03215-3"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Altieri, R., Barbagallo, D., Certo, F., Broggi, G., Ragusa, M., Di Pietro, C., Caltabiano, R., Magro, G., Peschillo, S., and Purrello, M. (2021). Peritumoral Microenvironment in High-Grade Gliomas: From FLAIRectomy to Microglia-Glioma Cross-Talk. Brain Sci., 11.","DOI":"10.3390\/brainsci11020200"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1002\/jcp.25592","article-title":"Overexpression of Large-Conductance Calcium-Activated Potassium Channels in Human Glioblastoma Stem-Like Cells and Their Role in Cell Migration","volume":"232","author":"Rosa","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Tagliaferro, M., Rosa, P., Bellenchi, G.C., Bastianelli, D., Trotta, R., Tito, C., Fazi, F., Calogero, A., and Ponti, D. (2022). Nucleolar localization of the ErbB3 receptor as a new target in glioblastoma. BMC Mol. Cell Biol., 23.","DOI":"10.1186\/s12860-022-00411-y"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3389\/fnagi.2018.00363","article-title":"Heme oxygenase-1 and brain oxysterols metabolism are linked to Egr-1 expression in aged mice cortex, but not in hippocampus","volume":"10","author":"Rosa","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ponti, D., Bastianelli, D., Rosa, P., Pacini, L., Ibrahim, M., Rendina, E.A., Ragona, G., and Calogero, A. (2015). The expression of B23 and EGR1 proteins is functionally linked in tumor cells under stress conditions. BMC Cell Biol., 16.","DOI":"10.1186\/s12860-015-0073-5"},{"key":"ref_61","first-page":"e4440","article-title":"Intranasal administration of CNS therapeutics to awake mice","volume":"74","author":"Hanson","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1093\/hmg\/ddy153","article-title":"Stimulation of S1PR 5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington\u2019s disease","volume":"27","author":"Castaldo","year":"2018","journal-title":"Hum. Mol. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/9563\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:14:21Z","timestamp":1760141661000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/9563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,24]]},"references-count":62,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms23179563"],"URL":"https:\/\/doi.org\/10.3390\/ijms23179563","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,24]]}}}