Elsherbiny Marwa E, Shaaban Mohammed, El-Tohamy Rana, Elkholi Islam E, Hammam Olfat Ali, Magdy Mona, Allalunis-Turner Joan, Emara Marwan
Department of Pharmacology and Toxicology, Ahram Canadian University, 6th of October, Egypt.
Center for Aging and Associated Diseases, Zewail City of Science, Technology and Innovation, 6th of October, Egypt.
Front Oncol. 2021 Apr 30;11:590771. doi: 10.3389/fonc.2021.590771. eCollection 2021.
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).
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.
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.
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.
肌红蛋白（MB）在癌症生长和转移中日益被视为关键因素。低氧张力通常与高侵袭性和复发性癌症相关，已表明其可调节多种癌症（如肺癌、颈部癌、前列腺癌和乳腺癌）中MB的表达。然而，MB是否有助于脑癌尤其是多形性胶质母细胞瘤（GBM）的生长和扩散尚不清楚。
在此，我们研究了MB在多器官肿瘤、脑肿瘤和GBM肿瘤以及各自癌旁正常组织的人体组织微阵列中的表达，及其与缺氧标志物碳酸酐酶IX（CAIX）和乳酸脱氢酶A（LDHA）的相关性。还评估了MB蛋白表达与肿瘤分级之间的相关性。
我们发现MB蛋白在多种癌症、良性肿瘤、癌旁正常组织、增生组织样本和正常脑组织中均有表达，低氧张力可调节不同脑癌（包括GBM）中MB蛋白的表达。在GBM中还观察到核内LDHA免疫反应性增强。最后，我们首次报道了MB表达与脑肿瘤分级之间呈正相关。
我们的数据表明，缺氧调节不同脑癌（包括GBM）中MB的表达，且其表达与更具侵袭性的表型相关，这一点通过与脑肿瘤分级的正相关得以体现。此外，基于仅在GBM中观察到的核内表达增强，还提示核内LDHA在促进侵袭性肿瘤表型方面发挥作用。
