{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:10:11Z","timestamp":1791382211980,"version":"4.3.3"},"reference-count":98,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003500","name":"University of Padova, Italy","doi-asserted-by":"publisher","award":["DOR2215418\/22"],"award-info":[{"award-number":["DOR2215418\/22"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome. The aim of this systematic, narrative review was to assess the level of knowledge on TME implicated in the biology, behavior, and prognosis of sporadic VSs. A search (updated to November 2022) was run in Scopus, PubMed, and Web of Science electronic databases according to the PRISMA guidelines, retrieving 624 titles. After full-text evaluation and application of inclusion\/exclusion criteria, 37 articles were included. VS microenvironment is determined by the interplay of a dynamic ecosystem of stromal and immune cells which produce and remodel extracellular matrix, vascular networks, and promote tumor growth. However, evidence is still conflicting. Further studies will enhance our understanding of VS biology by investigating TME-related biomarkers able to predict tumor growth and recognize immunological and molecular factors that could be potential therapeutic targets for medical treatment.<\/jats:p>","DOI":"10.3390\/ijms24076522","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T02:30:20Z","timestamp":1680229820000},"page":"6522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Tumor Microenvironment in Sporadic Vestibular Schwannoma: A Systematic, Narrative Review"],"prefix":"10.3390","volume":"24","author":[{"given":"Diego","family":"Cazzador","sequence":"first","affiliation":[{"name":"Otolaryngology Section, Department of Neuroscience DNS, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3291-8567","authenticated-orcid":false,"given":"Laura","family":"Astolfi","sequence":"additional","affiliation":[{"name":"Bioacoustics Research Laboratory, Department of Neuroscience DNS, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3687-8814","authenticated-orcid":false,"given":"Antonio","family":"Daloiso","sequence":"additional","affiliation":[{"name":"Otolaryngology Section, Department of Neuroscience DNS, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Tealdo","sequence":"additional","affiliation":[{"name":"Otolaryngology Section, Department of Neuroscience DNS, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7336-5041","authenticated-orcid":false,"given":"Edi","family":"Simoni","sequence":"additional","affiliation":[{"name":"Bioacoustics Research Laboratory, Department of Neuroscience DNS, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Mazzoni","sequence":"additional","affiliation":[{"name":"Otolaryngology Section, Department of Neuroscience DNS, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Zanoletti","sequence":"additional","affiliation":[{"name":"Otolaryngology Section, Department of Neuroscience DNS, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8751-0588","authenticated-orcid":false,"given":"Gino","family":"Marioni","sequence":"additional","affiliation":[{"name":"Phoniatrics and Audiology Unit, Department of Neuroscience DNS, University of Padova, 31100 Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1159\/000331394","article-title":"What is the site of origin of cochleovestibular schwannomas?","volume":"17","author":"Roosli","year":"2012","journal-title":"Audiol. Neurootol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1056\/NEJMra2020394","article-title":"Vestibular schwannomas","volume":"384","author":"Carlson","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"981","DOI":"10.2147\/CLEP.S218670","article-title":"Epidemiology of vestibular schwannomas\u2014Prospective 40-year data from an unselected national cohort","volume":"11","author":"Reznitsky","year":"2019","journal-title":"Clin. Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"384","DOI":"10.14639\/0392-100X-1756","article-title":"Multi-option therapy vs observation for small acoustic neuroma: Hearing-focused management","volume":"38","author":"Zanoletti","year":"2018","journal-title":"Acta Otorhinol. Ital."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"481","DOI":"10.14639\/0392-100X-N2322","article-title":"Early surgery and definitive cure in small sporadic vestibular schwannoma","volume":"42","author":"Zanoletti","year":"2022","journal-title":"Acta Otorhinol. Ital."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1097\/MAO.0000000000003608","article-title":"Early Translabyrinthine surgery for small- and medium-sized vestibular schwannomas: Consecutive cohort analysis of outcomes","volume":"43","author":"Zanoletti","year":"2022","journal-title":"Otol. Neurotol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3171\/2017.2.JNS162287","article-title":"Translabyrinthine microsurgical resection of small vestibular schwannomas","volume":"129","author":"Schwartz","year":"2018","journal-title":"J. Neurosurg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"579","DOI":"10.3171\/2012.9.JNS12919","article-title":"Long-term hearing outcomes following stereotactic radiosurgery for vestibular schwannoma: Patterns of hearing loss and variables influencing audiometric decline","volume":"118","author":"Carlson","year":"2013","journal-title":"J. Neurosurg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1097\/MAO.0000000000002312","article-title":"Vestibular schwannoma tumor size is associated with acute vestibular symptoms after gamma knife therapy","volume":"40","author":"Lee","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e83","DOI":"10.1097\/MAO.0000000000002401","article-title":"Factors associated with facial nerve paresis following gamma knife for vestibular schwannoma","volume":"41","author":"Lerner","year":"2020","journal-title":"Otol. Neurotol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s11060-019-03234-8","article-title":"Efficacy and safety of bevacizumab for vestibular schwannoma in neurofibromatosis type 2: A systematic review and meta-analysis of treatment outcomes","volume":"144","author":"Lu","year":"2019","journal-title":"J. Neurooncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.neuchi.2016.09.004","article-title":"Medical treatment in neurofibromatosis type 2. Review of the literature and presentation of clinical reports","volume":"64","author":"Goutagny","year":"2018","journal-title":"Neurochirurgie"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gugel, I., Kluwe, L., Zipfel, J., Teuber, C., Tatagiba, M., Mautner, V.F., Schuhmann, M.U., and Grimm, F. (2019). Minimal effect of bevacizumab treatment on residual vestibular schwannomas after partial resection in young neurofibromatosis type 2 patients. Cancers, 11.","DOI":"10.3390\/cancers11121862"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s12307-012-0124-9","article-title":"The immune microenvironment of human tumors: General significance and clinical impact","volume":"6","author":"Fridman","year":"2013","journal-title":"Cancer Microenviron."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the crime: Functions of cells recruited to the tumor microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/MAO.0000000000000189","article-title":"Aspirin intake correlates with halted growth of sporadic vestibular schwannoma in vivo","volume":"35","author":"Kandathil","year":"2014","journal-title":"Otol. Neurotol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1002\/lary.27114","article-title":"Aspirin does not prevent growth of vestibular schwannomas: A case-control study","volume":"128","author":"MacKeith","year":"2018","journal-title":"Laryngoscope"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2014.12.007","article-title":"Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannomas","volume":"166","author":"Dilwali","year":"2015","journal-title":"Transl. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Page, M.J., McKenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., Shamseer, L., Tetzlaff, J.M., Akl, E.A., and Brennan, S.E. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. PLoS Med., 18.","DOI":"10.1371\/journal.pmed.1003583"},{"key":"ref_20","unstructured":"NHLBI NIH (2022, November 15). Study Quality Assessment Tools, Available online: https:\/\/www.nhlbi.nih.gov\/health-topics\/study-quality-assessment-tools."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1001\/archoto.2009.79","article-title":"p73 expression and function in vestibular schwannoma","volume":"135","author":"Ahmad","year":"2009","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/MAO.0b013e3182009665","article-title":"Potential role of imatinib mesylate (Gleevec, STI-571) in the treatment of vestibular schwannoma","volume":"32","author":"Altuna","year":"2011","journal-title":"Otol. Neurotol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s13046-022-02473-4","article-title":"Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology","volume":"41","author":"Amit","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9940","DOI":"10.18632\/oncotarget.24119","article-title":"CXCR4: A new player in vestibular schwannoma pathogenesis","volume":"9","author":"Breun","year":"2018","journal-title":"Oncotarget"},{"key":"ref_25","first-page":"1856","article-title":"ADAM9: A novel player in vestibular schwannoma pathogenesis","volume":"19","author":"Breun","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1080\/00016480310005101","article-title":"Expression of angiogenic growth factors in acoustic neurinoma","volume":"123","author":"Brieger","year":"2003","journal-title":"Acta Oto-Laryngol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1017\/S0022215107000229","article-title":"Expression and clinical significance of Ki-67, oestrogen and progesterone receptors in acoustic neuroma","volume":"122","author":"Cafer","year":"2008","journal-title":"J. Laryngol. Otol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/00129492-200501000-00017","article-title":"VEGF and VEGF receptor-1 concentration in vestibular schwannoma homogenates correlates to tumor growth rate","volume":"26","author":"Werther","year":"2005","journal-title":"Otol. Neurotol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s00428-012-1236-9","article-title":"Intratumoral hemorrhage, vessel density, and the inflammatory reaction contribute to volume increase of sporadic vestibular schwannomas","volume":"460","author":"Hogendoorn","year":"2012","journal-title":"Virchows Arch."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00428-018-2503-1","article-title":"M-CSF and IL-34 expression as indicators for growth in sporadic vestibular schwannoma","volume":"474","author":"Hogendoorn","year":"2019","journal-title":"Virchows Arch."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1097\/00129492-200405000-00026","article-title":"Co-expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor in vestibular schwannoma","volume":"25","author":"Diensthuber","year":"2004","journal-title":"Otol. Neurotol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/000164801300043262","article-title":"Immunolocalization of erythropoietin and erythropoietin receptor in vestibular schwannoma","volume":"121","author":"Dillard","year":"2001","journal-title":"Acta Otolaryngol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1097\/MAO.0b013e31828048ec","article-title":"Sporadic vestibular schwannomas associated with good hearing secrete higher levels of fibroblast growth factor 2 than those associated with poor hearing irrespective of tumor size","volume":"34","author":"Dilwali","year":"2013","journal-title":"Otol. Neurotol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, V.M., Suhm, E.M., Ries, V., Skardelly, M., Tabatabai, G., Tatagiba, M., Schittenhelm, J., and Behling, F. (2021). Macrophage and lymphocyte infiltration is associated with volumetric tumor size but not with volumetric growth in the T\u00fcbingen schwannoma cohort. Cancers, 13.","DOI":"10.3390\/cancers13030466"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1017\/S0022215115001735","article-title":"Role of cyclins D1 and D3 in vestibular schwannoma","volume":"130","author":"Jabbour","year":"2016","journal-title":"J. Laryngol. Otol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1477-5751-8-9","article-title":"Expression of estrogen and progesterone receptors in vestibular schwannomas and their clinical significance","volume":"8","author":"Jaiswal","year":"2009","journal-title":"J. Negat. Res. Biomed."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1001\/archotol.1990.01870020078020","article-title":"Estrogen and progesterone receptors in acoustic neuromas","volume":"116","author":"Klinken","year":"1990","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1097\/MAO.0b013e31814b2787","article-title":"Expression of vascular endothelial growth factor and basic fibroblast growth factor in sporadic vestibular schwannomas correlates to growth characteristics","volume":"28","author":"Koutsimpelas","year":"2007","journal-title":"Otol. Neurotol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1159\/000346238","article-title":"The VEGF\/VEGF-R axis in sporadic vestibular schwannomas correlates with irradiation and disease recurrence","volume":"74","author":"Koutsimpelas","year":"2012","journal-title":"ORL J. Otorhinolaryngol. Relat. Spec."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s11060-009-0063-6","article-title":"BDNF mRNA expression is significantly upregulated in vestibular schwannomas and correlates with proliferative activity","volume":"98","author":"Kramer","year":"2010","journal-title":"J. Neurooncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1080\/00016480050218681","article-title":"Clinicopathologic growth factors in vestibular schwannomas: A morphologic and immunohistochemical study of 69 tumors","volume":"120","author":"Crebassa","year":"2000","journal-title":"Acta Otolaryngol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/MAO.0b013e3182001cc8","article-title":"Cyclin D1 expression and facial function outcome after vestibular schwannoma surgery","volume":"32","author":"Lassaletta","year":"2011","journal-title":"Otol Neurotol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Leisz, S., Klause, C.H., Vital Dos Santos, T., Haenel, P., Scheer, M., Simmermacher, S., Mawrin, C., Strauss, C., Scheller, C., and Rampp, S. (2022). Vestibular schwannoma volume and tumor growth correlates with macrophage marker expression. Cancers, 14.","DOI":"10.3390\/cancers14184429"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.3171\/2020.3.JNS193230","article-title":"The microenvironment in sporadic and neurofibromatosis type II-related vestibular schwannoma: The same tumor or different? A comparative imaging and neuropathology study","volume":"134","author":"Lewis","year":"2020","journal-title":"J. Neurosurg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.prp.2006.12.007","article-title":"Expression of transforming growth factor-beta receptor type 1 and type 2 in human sporadic vestibular Schwannoma","volume":"203","author":"Mawrin","year":"2007","journal-title":"Pathol. Res. Pract."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"152648","DOI":"10.1016\/j.prp.2019.152648","article-title":"Endoglin-based assessment of neoangiogenesis in sporadic VIII cranial nerve schwannoma","volume":"215","author":"Marioni","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e319","DOI":"10.5301\/ijbm.5000263","article-title":"YAP, TAZ and AREG expression in eighth cranial nerve schwannoma","volume":"32","author":"Martini","year":"2017","journal-title":"Int. J. Biol. Markers"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3109\/00016489609137712","article-title":"Angiogenesis from the eighth cranial nerve to vestibular schwannomas","volume":"116","author":"Matsunaga","year":"1996","journal-title":"Acta Otolaryngol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1078\/0344-0338-00340","article-title":"Expression pattern of apoptotic markers in vestibular schwannomas","volume":"198","author":"Mawrin","year":"2002","journal-title":"Pathol. Res. Pract."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/lary.20834","article-title":"Angiogenesis in vestibular schwannomas: Expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1","volume":"120","author":"Werther","year":"2010","journal-title":"Laryngoscope"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"866","DOI":"10.3171\/jns.2007.106.5.866","article-title":"Cystic vestibular schwannomas: A possible role of matrix metalloproteinase-2 in cyst development and unfavorable surgical outcome","volume":"106","author":"Moon","year":"2007","journal-title":"J. Neurosurg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/01.mlg.0000195076.05466.6c","article-title":"Cyclin D(1) and D(3) expression in vestibular schwannomas","volume":"116","author":"Neff","year":"2006","journal-title":"Laryngoscope"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.3171\/2019.7.JNS19879","article-title":"Predominance of M1 subtype among tumor-associated macrophages in phenotypically aggressive sporadic vestibular schwannoma","volume":"133","author":"Perry","year":"2019","journal-title":"J. Neurosurg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"107770","DOI":"10.1016\/j.heares.2019.07.007","article-title":"NLRP3 inflammasome activation in human vestibular schwannoma: Implications for tumor-induced hearing loss","volume":"381","author":"Sagers","year":"2019","journal-title":"Hear. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11060-005-2886-0","article-title":"Aggressive vestibular schwannomas showing postoperative rapid growth\u2014Their association with decreased p27 expression","volume":"75","author":"Seol","year":"2005","journal-title":"J. Neurooncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"737","DOI":"10.3892\/mmr.2015.3415","article-title":"Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue","volume":"12","author":"Taurone","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1016\/j.wneu.2020.07.208","article-title":"Immunohistochemical profiles of matrix metalloproteinases and vascular endothelial growth factor overexpression in the Antoni B area of vestibular schwannomas","volume":"144","author":"Xia","year":"2020","journal-title":"World Neurosurg."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Dzobo, K., Senthebane, D.A., and Dandara, C. (2023). The tumor microenvironment in tumorigenesis and therapy resistance revisited. Cancers, 15.","DOI":"10.3390\/cancers15020376"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"105982","DOI":"10.1016\/j.oraloncology.2022.105982","article-title":"Tumor-stroma ratio, neoangiogenesis and prognosis in laryngeal carcinoma. A pilot study on preoperative biopsies and matched surgical specimens","volume":"132","author":"Alessandrini","year":"2022","journal-title":"Oral Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1056\/NEJM197111182852108","article-title":"Tumor angiogenesis: Therapeutic implications","volume":"285","author":"Folkman","year":"1971","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1084\/jem.133.2.275","article-title":"Isolation of a tumor factor responsible for angiogenesis","volume":"133","author":"Folkman","year":"1971","journal-title":"J. Exp. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1365-2559.2010.03664.x","article-title":"Neoangiogenesis in laryngeal carcinoma: Angiogenin and CD105 expression is related to carcinoma recurrence rate and disease-free survival","volume":"57","author":"Marioni","year":"2010","journal-title":"Histopathology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0092-8674(00)80108-7","article-title":"Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis","volume":"9","author":"Hanahan","year":"1996","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s004010050591","article-title":"Expression and distribution of vascular endothelial growth factor protein in human brain tumors","volume":"93","author":"Pietsch","year":"1997","journal-title":"Acta Neuropathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s004010050919","article-title":"Expression of vascular endothelial growth factor in human brain tumors","volume":"96","author":"Nishikawa","year":"1998","journal-title":"Acta Neuropathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/74664","article-title":"Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy","volume":"6","author":"Schratzberger","year":"2000","journal-title":"Nat. Med."},{"key":"ref_67","first-page":"1","article-title":"Acoustic neuroma\/vestibular schwannoma in vivo and in vitro growth models. A clinical and experimental study","volume":"530","author":"Charabi","year":"1997","journal-title":"Acta Otolaryngol."},{"key":"ref_68","first-page":"30","article-title":"Expression of Ki-67 antigen and vascular endothelial growth factor in sporadic and neurofibromatosis type 2-associated schwannomas","volume":"22","author":"Saito","year":"2003","journal-title":"Clin. Neuropathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1097\/00005537-200312000-00014","article-title":"Immunohistochemical demonstration of VEGF in vestibular schwannomas correlates to tumor growth rate","volume":"113","author":"Baandrup","year":"2003","journal-title":"Laryngoscope"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1080\/00016480410023047","article-title":"Endoglin (CD105) expression in head and neck basaloid squamous cell carcinoma","volume":"125","author":"Marioni","year":"2005","journal-title":"Acta Otolaryngol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1097\/MAO.0b013e3181e40e4f","article-title":"B7-H1 expression in vestibular schwannomas","volume":"31","author":"Archibald","year":"2010","journal-title":"Otol. Neurotol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1189\/jlb.0609385","article-title":"Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation","volume":"86","author":"Solinas","year":"2009","journal-title":"J. Leuk. Biol."},{"key":"ref_73","first-page":"23","article-title":"Tissue-resident versus monocyte-derived macrophages in the tumor microenvironment","volume":"1865","author":"Lahmar","year":"2016","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10394","DOI":"10.1074\/jbc.M200083200","article-title":"Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization","volume":"277","author":"Kissil","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1083\/jcb.200503165","article-title":"Merlin\/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane","volume":"171","author":"Okada","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gad.274027.115","article-title":"Mechanisms of Hippo pathway regulation","volume":"30","author":"Meng","year":"2016","journal-title":"Genes Dev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e269","DOI":"10.1016\/j.wneu.2018.06.010","article-title":"Deregulation of the Hippo pathway promotes tumor cell proliferation through YAP activity in human sporadic vestibular schwannoma","volume":"117","author":"Zhao","year":"2018","journal-title":"World Neurosurg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/bpa.12125","article-title":"Schwannomas and their pathogenesis","volume":"24","author":"Hilton","year":"2014","journal-title":"Brain Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fnmol.2017.00038","article-title":"Molecular mechanisms involved in schwann cell plasticity","volume":"10","author":"Boerboom","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1582-4934.2005.tb00355.x","article-title":"Matrix metalloproteinases and angiogenesis","volume":"9","author":"Rundhaug","year":"2005","journal-title":"J. Cell Mol. Med."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Cabral-Pacheco, G.A., Garza-Veloz, I., La Rosa, C.C.-D., Ramirez-Acu\u00f1a, J.M., Perez-Romero, B.A., Guerrero-Rodriguez, J.F., Martinez-Avila, N., and Martinez-Fierro, M.L. (2020). The roles of matrix metalloproteinases and their inhibitors in human diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249739"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.cardiores.2005.12.002","article-title":"Structure and function of matrix metalloproteinases and TIMPs","volume":"69","author":"Nagase","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1083\/jcb.132.4.717","article-title":"MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains","volume":"132","author":"Weskamp","year":"1996","journal-title":"J. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4728","DOI":"10.1158\/0008-5472.CAN-04-4449","article-title":"A secreted form of ADAM9 promotes carcinoma invasion through tumor-stromal interactions","volume":"65","author":"Mazzocca","year":"2005","journal-title":"Cancer Res."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Fan, X., Wang, Y., Zhang, C., Liu, L., Yang, S., Wang, Y., Lu, X., Qian, Z., Fang, S., and Qiao, H. (2016). ADAM9 expression is associated with glioma tumor grade and histological type, and acts as a prognostic factor in lower-grade gliomas. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091276"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/1878-0261.12426","article-title":"ADAM9 contributes to vascular invasion in pancreatic ductal adenocarcinoma","volume":"13","author":"Oria","year":"2019","journal-title":"Mol. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"18599","DOI":"10.1038\/srep18599","article-title":"Secreted factors from human vestibular schwannomas can cause cochlear damage","volume":"5","author":"Dilwali","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/ni.2919","article-title":"The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response","volume":"15","author":"Gomez","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e220174","DOI":"10.1530\/JME-22-0174","article-title":"RISING STARS: Hormonal regulation of the breast cancer microenvironment","volume":"70","author":"Boyle","year":"2023","journal-title":"J. Mol. Endocrinol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0090-3019(81)90023-9","article-title":"Estrogen receptors in acoustic neurilemmomas","volume":"15","author":"Kasantikul","year":"1981","journal-title":"Surg. Neurol."},{"key":"ref_91","first-page":"303","article-title":"Sex hormone receptors in intracranial tumors and normal brain","volume":"13","author":"Whittle","year":"1987","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/0002-9378(74)90212-9","article-title":"Acoustic neuroma in the last months of pregnancy","volume":"119","author":"Allen","year":"1974","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1177\/019459989010300307","article-title":"Estrogen and progesterone binding in acoustic neuroma tissue","volume":"103","author":"Monsell","year":"1990","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1288\/00005537-199507000-00005","article-title":"Acoustic schwannomas in pregnancy: A DNA flow cytometric, steroid hormone receptor and proliferation marker study","volume":"105","author":"Beatty","year":"1995","journal-title":"Laryngoscope"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/BF01844749","article-title":"Hormone receptors in vestibular schwannomas","volume":"139","author":"Carroll","year":"1997","journal-title":"Acta Neurochir."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1017\/S0022215100114197","article-title":"Oestrogen and progesterone receptors in acoustic neuroma","volume":"104","author":"Curley","year":"1990","journal-title":"J. Laryngol. Otol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1055\/s-0028-1096198","article-title":"Immunohistochemical investigation of hormonal receptors and vascular endothelial growth factor concentration in vestibular schwannoma","volume":"18","author":"Dalgorf","year":"2008","journal-title":"Skull Base"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/s100249900103","article-title":"Immunohistochemical localization of erythropoietin and its receptor in the developing human brain","volume":"2","author":"Juul","year":"1999","journal-title":"Ped. Dev. Path."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6522\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:07:41Z","timestamp":1760123261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,30]]},"references-count":98,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076522"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076522","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,30]]}}}