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Article

Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?

  • Authors:
    • Rana El‑Tohamy
    • Islam Elkholi
    • Marwa E. Elsherbiny
    • Mona Magdy
    • Olfat Hammam
    • Joan Allalunis‑Turner
    • Marwan Emara
  • View Affiliations / Copyright

    Affiliations: Center for Aging and Associated Diseases, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza 12578, Egypt, Department of Pharmacology and Toxicology, Ahram Canadian University, 6th of October City, Giza 12566, Egypt, Department of Pathology, Theodor Bilharz Research Institute (TBRI), Imbaba, Giza 12411, Egypt, Department of Oncology, University of Alberta and Alberta Health Services, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
  • Pages: 975-985
    |
    Published online on: January 23, 2020
       https://doi.org/10.3892/or.2020.7479
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Abstract

Glioblastoma multiforme (GBM) is the most aggressive human brain cancer. Little is known regarding how these cells adapt to the harsh tumor microenvironment, and consequently survive and resist various treatments. Myoglobin (MB), the oxygen‑binding hemoprotein, has been shown to be ectopically expressed in different human cancers and cell lines, and its expression is hypothesized to be an adaptation mechanism to hypoxia. The aim of the present study was to determine whether cancer‑related and hypoxia‑responsive MB mRNA splice variants are expressed in human GBM cells and glioblastoma tumor xenografts, and whether their expression is induced by hypoxia and correlated with hypoxia markers [lactate dehydrogenase A (LDHA), glucose transporter 1 (GLUT1), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CAIX)]. Conventional reverse transcription (RT)‑PCR, DNA sequencing, RT‑quantitative PCR and immunohistochemistry were conducted to investigate MB expression in hypoxia‑sensitive (M010b, M059J) and ‑tolerant (M059K, M006xLo) GBM cell lines that also exhibit differential response towards radiation, rendering them a valuable translational GBM model. It was revealed that cancer‑related MB variants 9, 10, 11 and 13 were expressed in GBM cells under normoxia, and following hypoxia, their expression exhibited modest‑to‑significant upregulation that correlated with hypoxia markers. It was also demonstrated that MB was upregulated in hypoxic microregions of glioblastoma tumor xenografts that were stained in matched tumor regions of serial tumor sections with the hypoxia markers, pimonidazole, CAIX, VEGF and LDHA. The present study identified myoglobin as a potential contributor to the hypoxia adaptation and survival strategies of glioblastoma, and may explain the aggressiveness and frequent recurrence rates associated with GBM.
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Copy and paste a formatted citation
Spandidos Publications style
El‑Tohamy R, Elkholi I, Elsherbiny ME, Magdy M, Hammam O, Allalunis‑Turner J and Emara M: Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?. Oncol Rep 43: 975-985, 2020.
APA
El‑Tohamy, R., Elkholi, I., Elsherbiny, M.E., Magdy, M., Hammam, O., Allalunis‑Turner, J., & Emara, M. (2020). Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?. Oncology Reports, 43, 975-985. https://doi.org/10.3892/or.2020.7479
MLA
El‑Tohamy, R., Elkholi, I., Elsherbiny, M. E., Magdy, M., Hammam, O., Allalunis‑Turner, J., Emara, M."Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?". Oncology Reports 43.3 (2020): 975-985.
Chicago
El‑Tohamy, R., Elkholi, I., Elsherbiny, M. E., Magdy, M., Hammam, O., Allalunis‑Turner, J., Emara, M."Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?". Oncology Reports 43, no. 3 (2020): 975-985. https://doi.org/10.3892/or.2020.7479
Copy and paste a formatted citation
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Spandidos Publications style
El‑Tohamy R, Elkholi I, Elsherbiny ME, Magdy M, Hammam O, Allalunis‑Turner J and Emara M: Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?. Oncol Rep 43: 975-985, 2020.
APA
El‑Tohamy, R., Elkholi, I., Elsherbiny, M.E., Magdy, M., Hammam, O., Allalunis‑Turner, J., & Emara, M. (2020). Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?. Oncology Reports, 43, 975-985. https://doi.org/10.3892/or.2020.7479
MLA
El‑Tohamy, R., Elkholi, I., Elsherbiny, M. E., Magdy, M., Hammam, O., Allalunis‑Turner, J., Emara, M."Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?". Oncology Reports 43.3 (2020): 975-985.
Chicago
El‑Tohamy, R., Elkholi, I., Elsherbiny, M. E., Magdy, M., Hammam, O., Allalunis‑Turner, J., Emara, M."Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?". Oncology Reports 43, no. 3 (2020): 975-985. https://doi.org/10.3892/or.2020.7479
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