All-Trans Retinoic Acid Fosters the Multifarious U87MG Cell Line as a Model of Glioblastoma

Abstract

Glioblastoma multiforme (GBM) is a primary brain cancer of poor prognosis, with existing treatments remaining essentially palliative. Current GBM therapy fails due to rapid reappearance of the heterogeneous neoplasm, with models suggesting that the recurrent growth is from treatment-resistant glioblastoma stem-like cells (GSCs). Whether GSCs depend on survival/proliferative cues from their surrounding microenvironmental niche, particularly surrounding the leading edge after treatment remains unknown. Simulating human GBM in the laboratory relies on representative cell lines and xenograft models for translational medicine. Due to U87MG source discrepancy and differential proliferation responses to retinoic acid treatment, this study highlights the challenges faced by laboratory scientists working with this representative GBM cell line. Investigating the response to all trans-retinoic acid (ATRA) revealed its sequestering of the prominin-1 stem cell marker. ICAM-1 universally present throughout U87MG was enhanced by ATRA, of interest for chemotherapy targeting studies. ATRA triggered diverse expression patterns of long non-coding RNAs PARTICLE and GAS5 in the leading edge and established monolayer growth zone microenvironment. Karyotyping confirmed the female origin of U87MG sourced from Europe. Passaging U87MG revealed the presence of chromosomal anomalies reflective of structural genomic alterations in this glioblastoma cell line. All evidence considered, this study exposes further phenotypic nuances of U87MG which may belie researchers seeking data contributing towards the elusive cure for GBM.

Biomolecules to Biomarkers? U87MG Marker Evaluation on the Path towards Glioblastoma Multiforme Pathogenesis

“…Recently, we validated and deciphered the phenotypic nuances of the GBM cell line U87MG (ECACC 89081402; p53 wild-type; methylated MGMT promoter) [ 2 , 26 , 27 ]. Findings revealed that exposure to all-trans retinoic acid (ATRA) attenuated the expression of prominin-1 (CD133), a stem cell marker.…”

“…Findings revealed that exposure to all-trans retinoic acid (ATRA) attenuated the expression of prominin-1 (CD133), a stem cell marker. Histochemical evidence highlighted the presence of prominin-1 in the cytoplasm but its absence in perinuclear space [ 26 ]. Conversely, the intercellular adhesion molecule-1 (ICAM-1; CD54), a chemotherapeutic targeting molecule, showed increased expression in response to ATRA [ 26 ].…”

“…Histochemical evidence highlighted the presence of prominin-1 in the cytoplasm but its absence in perinuclear space [ 26 ]. Conversely, the intercellular adhesion molecule-1 (ICAM-1; CD54), a chemotherapeutic targeting molecule, showed increased expression in response to ATRA [ 26 ]. ICAM-1 is regarded as an important mediator in tumor migration and invasion [ 28 , 29 ].…”

“…ICAM-1 is regarded as an important mediator in tumor migration and invasion [ 28 , 29 ]. The long non-coding RNA (lncRNA) PARTICLE , a negative regulator of tumor suppressors, demonstrated significantly high expressivity in early passaged U87MG exposed to ATRA with transcripts confined to the leading edge of the microenvironment [ 26 ]. Nevertheless, low transcript levels of the lncRNA GAS5 were noted in this location under similar conditions [ 26 ], reflective of its tumor suppressor status and association with overall GBM patient survival [ 30 ].…”

Interactions of Nanoscale Self-Assembled Peptide-Based Assemblies with Glioblastoma Cell Models and Spheroids

“…The Aze5-angiopep-2 nanoassemblies were then functionalized with A-COOP-K peptide for targeting of two glioblastoma cell models, namely, U-87-MG and U-138-MG glioblastoma cells. Both these cell lines have been utilized as models for examining glioblastoma cell interactions in previous studies. , Supramolecular nanofibrillar structures were formed that efficiently entrapped the chemotherapeutic drug doxorubicin (DOX) and the interactions of the drug entrapped nanoassemblies with glioblastoma cells were examined. Furthermore, three-dimensional spheroids of the cells were grown, and the internalization of the drug entrapped nanoassemblies was explored.…”