Abstract
Glioblastoma multiforme (GBM) also categorized as a grade IV astrocytoma, is an aggressive brain tumor which invades the surrounding brain tissue. Hyperthermia is known to be effective for chemo-radiotherapy to sensitize cancer cells to radiation as a treatment option for patients with GBM. The current study was performed in order to assess and compare the properties of the astrocyte and cancer stem cells isolated from glioblastoma exposed to hyperthermia. Astrocytes and cancer stem cells were isolated from human glioblastoma tissue. Glioblastoma tissues were digested and cultured in culture medium supplemented with B27, basic fibroblast growth factor and epidermal growth factor. The morphology and specific markers were evaluated in astrocyte and cancer stem cell of human glioblastoma through immunocytochemistry and quantitative real-time RT-PCR. The multipotentiality of cancer stem cells was presented using differentiation potential into neurons, oligodendrocytes, and astrocytes. For hyperthermia, cells were exposed to temperatures at 4246 °C for 1 h using a water bath. Cell survival rate by MTT assay and apoptosis using quantitative real-time RT-PCR and western blot were evaluated. Results demonstrated that there were two morphology types in cell culture including epithelioid morphology and fibroblastic morphology. Astrocytes were confirmed via expression of the Glial fibrillary acidic protein (GFAP) protein; whereas, cancer stem cells (CSCs) were round and floating in the culture medium. Immunocytochemical staining indicated that nestin, CD133 and SRY-box 2 (SOX2) antigens were positively expressed in primary neurospheres. Results indicated that cancer stem cells of glioblastoma are multipotent and are able to differentiate into neurons, oligodendrocytes, and astrocytes. The current study obtained evidence via apoptosis evaluation that CSCs are resistant to hyperthermia when compared to astrocytes isolated from glioblastoma. Furthermore, hyperthermia was demonstrated to decrease cell resistance, which may be effective for chemo-radiotherapy to sensitize cancer cells to radiation. Taken together, CSCs of glioblastoma could be used as a powerful tool for evaluating the tumorigenesis process in the brain and developing novel therapies for treatment of GBM.
Highlights
Glioblastoma multiforme is an aggressive and lethal brain tumor among the various human cancers because this tumor has a recurrence potential [1]
We addressed that CSCs isolated from glioblastoma can differentiate to other cells and we indicated that cancer stem cells of human glioblastoma are more resistant to hyperthermia than astrocytes isolated from glioblastoma
Morphology and identification of neurospheres derived from human glioblastoma multiforme We isolated CSCs from human glioblastoma core zone (Fig. 1, A)
Summary
Glioblastoma multiforme is an aggressive and lethal brain tumor among the various human cancers because this tumor has a recurrence potential [1]. Evidence in research suggests that is CSCs likely to be responsible for high treatment resistance of glioblastoma and lead to tumor recurrence; but leads to an increase in mortality due to DNA repair potential to be increased in CSCs [9]. Studies have suggested that CSCs depend on the microenvironmental conditions of the brain for growth and differentiation [10, 11] Another important factor that may play a principle role in the formation of glioblastoma is the cell of origin. Glioblastoma tumors are composed of heterogeneous cells that include CSCs and astrocytes that, together perhaps, lead to an abundance of problems that makes these patients resistant to treatment [12]. Each area of a gliblastoma has specific properties, conditions and function
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