Abstract
BackgroundMyoglobin (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).MethodsHere 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.ResultsWe 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.ConclusionOur 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.
Highlights
Glioblastoma multiforme (GBM) is the most common primary brain cancer and is associated with poor prognosis [1]
We screened each group of tissue microarrays (TMA): multiple organ tumors (39 cases/43 cores), different brain tumors (40 cases/80 cores), and GBM tumors (40 cases/80 cores), each with its respective cancer-adjacent normal tissues (CANT) for CAIX, lactate dehydrogenase A (LDHA), and MB protein expression
Positive MB immunostaining was observed in all benign tumors and hyperplastic samples from cirrhotic liver and prostate
Summary
Glioblastoma multiforme (GBM) is the most common primary brain cancer and is associated with poor prognosis [1]. The hypoxia-tolerant cell lines (M006x and M059K) were capable of reducing their oxygen consumption rates and maintaining their clonogenic potential after 4 days of hypoxia (0.6% oxygen) while the hypoxia-sensitive cells (M010b) failed to reduce their oxygen consumption rates and to maintain their clonogenic potential [6] These observations potentially explain GBM recurrence and ability to adapt to hypoxic tumor microenvironment, yet, the underlying hypoxia-adaptation mechanisms are still not clear. 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 It is not yet known whether it contributes to the growth and spread of brain cancers especially Glioblastoma multiforme (GBM)
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