Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells

Abstract

Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.

Hemoglobins, Hemorphins, and 11p15.5 Chromosomal Region in Cancer Biology and İmmunity with Special Emphasis for Brain Tumors

“…91,92 Thereafter, analyses confirmed the presence of different HBs (α, β, γ, δ, ζ, and ε) in human GBM cells under normal conditions, indicating reactivation of fetal and embryonic genes and their potential in inherent resistance of GBMs. 93 However, expression of these HBs did not differ between GBM cells with differing resistances to hypoxia and radiation. 93 Nonetheless, these results were obtained from monolayer cultures that do not mimic the pathophysiologic features of tumors with differential distribution of hypoxic areas and cell-to-cell contacts.…”

“…93 However, expression of these HBs did not differ between GBM cells with differing resistances to hypoxia and radiation. 93 Nonetheless, these results were obtained from monolayer cultures that do not mimic the pathophysiologic features of tumors with differential distribution of hypoxic areas and cell-to-cell contacts. Changes in HB expressions with experimental hypoxia in GBM cell lines were also analyzed.…”

Advances in Hypoxia-Mediated Mechanisms in Hepatocellular Carcinoma

“…Recently, the expression of Ngb and its homologous Cygb were also investigated in various cancers. Emara et al (2010Emara et al ( , 2014 reported that Ngb/Cygb was widely expressed in many cancers through microarray analysis. However, Gorr et al (2011) reported that Ngb, but not Cygb, was elevated in only a few types of tumors.…”

Mammalian nerve globins in search of functions

“…The hypoxic upregulation of Hb expression in glioblastoma multiforme cells may be a part of a repertoire of active defense and adaptation mechanisms enabling these cells to acquire resistance to chemotherapy and radiotherapy. Therefore, new therapeutic strategies are required to interfere with Hb expression or function in glioblastoma multiforme cells .…”

“…Mammalian nerve globins colocalize not only in the brain and in the neuronal retina but also in different tissues and organs . The concentration of mammalian nerve globins is generally ∼1 μM ; Ngb has been found at relatively high concentration in neurons of the hypothalamus reaching high levels (from 100 to 200 μM) in the retina rod cells .…”