Response of human glioblastoma cells to hyperthermia: Cellular apoptosis and molecular events

Mansoureh Hashemi; Aida Abbasiazam; Saeed Oraee-Yazdani; Janice Lenzer

doi:10.1016/j.tice.2022.101751

Response of human glioblastoma cells to hyperthermia: Cellular apoptosis and molecular events

Tissue Cell. 2022 Apr:75:101751. doi: 10.1016/j.tice.2022.101751. Epub 2022 Feb 4.

Authors

Mansoureh Hashemi¹, Aida Abbasiazam², Saeed Oraee-Yazdani³, Janice Lenzer⁴

Affiliations

¹ Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: mansoureh.hashemi@sbmu.ac.ir.
² Biology Department, Queens College of the City University of New York, Queens, New York, USA; The Graduate Center of the City University of New York, New York, USA.
³ Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁴ The Graduate Center of the City University of New York, New York, USA.

PMID: 35144007
DOI: 10.1016/j.tice.2022.101751

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.

Keywords: Apoptosis; Astrocyte; Cancer stem cell; Glioblastoma multiforme; Hyperthermia.

MeSH terms

Apoptosis
Brain Neoplasms* / metabolism
Brain Neoplasms* / pathology
Brain Neoplasms* / therapy
Cell Line, Tumor
Glioblastoma* / metabolism
Humans
Hyperthermia, Induced*
Neoplastic Stem Cells / pathology