{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:44:56Z","timestamp":1773661496606,"version":"3.50.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T00:00:00Z","timestamp":1619740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010720","name":"Zewail City of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010720","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Myoglobin (MB) is increasingly recognized as a key player in cancer growth and metastasis. Low oxygen tensions, commonly associated with highly aggressive and recurrent cancers, have been shown to regulate its expression in several cancers such as lung, neck, prostate and breast cancer. However, it is not yet known whether it contributes to the growth and spread of brain cancers especially Glioblastoma multiforme (GBM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here we investigate the expression of MB, and its correlation with the hypoxia markers carbonic anhydrase IX (CAIX) and lactate dehydrogenase A (LDHA), in human tissue microarrays of multiple organ tumors, brain tumors, and GBM tumors, and their respective cancer-adjacent normal tissues. Correlation between MB protein expression and tumor grade was also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that MB protein is expressed in a wide variety of cancers, benign tumors, cancer-adjacent normal tissues, hyperplastic tissue samples and normal brain tissue, and low oxygen tensions modulate MB protein expression in different brain cancers, including GBM. Enhanced nuclear LDHA immune-reactivity in GBM was also observed. Finally, we report for the first time a positive correlation between MB expression and brain tumor grade.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that hypoxia regulate MB expression in different brain cancers (including GBM) and that its expression is associated with a more aggressive phenotype as indicated by the positive correlation with the brain tumor grade. Additionally, a role for nuclear LDHA in promoting aggressive tumor phenotype is also suggested based on enhanced nuclear expression which was observed only in GBM.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.590771","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T08:07:48Z","timestamp":1619770068000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Expression of Myoglobin in Normal and Cancer Brain Tissues: Correlation With Hypoxia Markers"],"prefix":"10.3389","volume":"11","author":[{"given":"Marwa E.","family":"Elsherbiny","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Shaaban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rana","family":"El-Tohamy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Islam E.","family":"Elkholi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olfat Ali","family":"Hammam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Magdy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Allalunis-Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwan","family":"Emara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/nu10040454","article-title":"Omega-3 and Omega-6 Fatty Acids Modulate Conventional and Atypical Protein Kinase C Activities in a Brain Fatty Acid Binding Protein Dependent Manner in Glioblastoma Multiforme","volume":"10","author":"Elsherbiny","year":"2018","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867324666170516123206","article-title":"Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review","volume":"24","author":"Batash","year":"2017","journal-title":"Curr Med Chem"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00707","article-title":"Improved Pathologic Diagnosis-Forecasting the Future in Glioblastoma","volume":"8","author":"Pisapia","year":"2018","journal-title":"Front Neurol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-10-33","article-title":"Hypoxic Regulation of Cytoglobin and Neuroglobin Expression in Human Normal and Tumor Tissues","volume":"10","author":"Emara","year":"2010","journal-title":"Cancer Cell Int"},{"key":"B5","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s12943-019-1089-9","article-title":"Role of Hypoxia in Cancer Therapy by Regulating the Tumor Microenvironment","volume":"18","author":"Jing","year":"2019","journal-title":"Mol Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690328","article-title":"Modulation of Oxygen Consumption Rate and Vascular Endothelial Growth Factor mRNA Expression in Human Malignant Glioma Cells by Hypoxia","volume":"80","author":"Allalunis-Turner","year":"1999","journal-title":"Br J Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.669","article-title":"Variable Presence of Hypoxia in M006 Human Glioma Spheroids and in Spheroids and Xenografts of Clonally Derived Sublines","volume":"78","author":"Franko","year":"1998","journal-title":"Br J Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1997.52","article-title":"Anomalous Patterns of Nitroimidazole Binding Adjacent to Necrosis in Human Glioma Xenografts: Possible Role of Decreased Oxygen Consumption","volume":"75","author":"Parliament","year":"1997","journal-title":"Br J Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011627","article-title":"Evolution of Hemoglobin and its Genes","volume":"2","author":"Hardison","year":"2012","journal-title":"Cold Spring Harbor Perspect Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/185422a0","article-title":"Structure of Myoglobin: A Three-Dimensional Fourier Synthesis At 2 A. 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