Establishment and characterization of a chemoresistant glioblastoma cell line from an Iraqi patient

ABSTRACT: Glioblastoma multiforme is a highly aggressive malignant primary brain tumor in humans, with poor prognosis. ANGM5 has been established from a cerebral glioblastoma multiforme in a 72-years-old Iraqi man who underwent surgery for an intracranial tumor in 2005. The morphology, growth kinetics, karyotype, immunocytochemistry and angiogenesis factors expression profile were studied. ANGM5 has been grown continuously for more than 200 serial passages in culture for the last 13 years. The cultured cells are elongated or multipolar in shape and the population doubling time is 28 hours. The karyotype is complex, and the chromosomal number varied between 39-114. ANGM5 is resistant to Temozolomide, cisplatin, vincristine and etoposide. This chemoresistance could be explained by the overexpression of the breast cancer resistance protein (BCRP) and MGMT. Immunocytochemistry analysis of glial markers demonstrated that cells are positive for glial fibrillary acidic protein (GFAP), and negative for nestin and calbindin. Protein microarray analysis showed high production of tissue inhibitor of metalloproteinase 2 (TIMP2) as well as other factors that are important for the invasiveness and aggressiveness of glioblastoma. ANGM5 is a useful addition to the cell lines currently available for study of the pathobiology and chemoresistance properties of glioblastoma multiforme and antitumor drug discovery. Angiogenesis signaling is being evaluated in new human Iraqi glioblastoma multiforme cell line. Here, we measured angiogenesis factors released by cancer cells in vitro. We find that glioblastoma up-regulates many proteins and metabolites during the logarithmic phase, suggesting initiation of their endo-vesiculo-membrane system. Importantly, GM-CSF and G-CSF as they increase angiogenesis through promoting endothelial cell function. Also, b-FGF which promote tumor growth and proliferation. Moreover, it showed up-regulation to inflammatory, and extracellular matrix proteins. These factors will help proliferating glioblastoma cells to overcome stress conditions, such as cytotoxic chemotherapy, serum deprivation, hypoxia in vitro and in vivo. These findings support other evidence of chemoresistance ability of this cell line named AMGN5 as it found to resist several types of conventional chemotherapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118960 | GEO | 2018/08/24

REPOSITORIES: GEO