Myoglobin Expression by Tumor Cells and Its Role in Progression of Malignancy

Abstract

The review considers the data available in the literature on myoglobin expression in various tumors and cell lines of non-muscle tumor cells and on the influence of hypoxia, reactive oxygen and nitrogen species, hormones, growth factors, gender, and age on this process. The effect of tumor myoglobin on cellular processes such as oxidative stress, inhibition of mitochondrial respiration by nitric oxide, and fatty acid metabolism is also analyzed, both during endogenous expression of small amounts (~1 μM) of myoglobin and overexpression of the protein (~150 μM) due to incorporation of the myoglobin gene into the tumor cell genome. It is concluded that hypoxia-induced intrinsic expression of low concentrations of myoglobin, due to its ability to utilize reactive oxygen and nitrogen species that can damage tumor cells, ensures their better survival by promoting tumor progression and metastasis. Accordingly, this expression of myoglobin is generally associated with a more aggressive tumor type, poor prognosis for the course and outcome of the disease, and may thus serve as a “marker” of an aggressive malignancy. In contrast, artificial overexpression of myoglobin can significantly inhibit tumor development and improve disease course by switching cancer cell metabolism from tumor-specific glycolysis to oxidative phosphorylation inherent in healthy tissue. Myoglobin overexpression may thus be an effective therapeutic tool in oncology.