Development of a patient-derived xenograft model of glioblastoma via intravitreal injection in mice

Abstract

Currently, the two primary patient-derived xenograft (PDX) models of glioblastoma are established through intracranial or subcutaneous injection. In this study, a novel PDX model of glioblastoma was developed via intravitreal injection to facilitate tumor formation in a brain-mimicking microenvironment with improved visibility and fast development. Glioblastoma cells were prepared from the primary and recurrent tumor tissues of a 39-year-old female patient. To demonstrate the feasibility of intracranial tumor formation, U-87 MG and patient-derived glioblastoma cells were injected into the brain parenchyma of Balb/c nude mice. Unlike the U-87 MG cells, the patient-derived glioblastoma cells failed to form intracranial tumors until 6 weeks after tumor cell injection. In contrast, the patient-derived cells effectively formed intraocular tumors, progressing from plaques at 2 weeks to masses at 4 weeks after intravitreal injection. The in vivo tumors exhibited the same immunopositivity for human mitochondria, GFAP, vimentin, and nestin as the original tumors in the patient. Furthermore, cells isolated from the in vivo tumors also demonstrated morphology similar to that of their parental cells and immunopositivity for the same markers. Overall, a novel PDX model of glioblastoma was established via the intravitreal injection of tumor cells. This model will be an essential tool to investigate and develop novel therapeutic alternatives for the treatment of glioblastoma.

XPO1-dependent nuclear export as a target for cancer therapy

“…The development of SINEs has enabled the translational application of nuclear export inhibitors as novel therapeutic agents. A number of SINE compounds have been tested extensively in preclinical settings, exhibiting efficacy in solid tumors [14,[70][71][72][73][74] and hematopoietic malignancies [75][76][77][78][79]. Among the investigated SINEs, KPT-330, KPT-8602, and SL-80 have been advanced to clinical trials.…”

HAX1 maintains the glioma progression in hypoxia through promoting mitochondrial fission

“… 1 , 2 Even though the traditional treatment methods (including surgical resection, radiotherapy and chemotherapy) have made considerable progress, the survival rate of glioma remains at a low level. 3 , 4 , 5 A better understanding of glioma that provides a new potential treatment to glioma needs a breakthrough.…”

Advances in Research of Adult Gliomas

“…Recently, a particular xenograft model using patient-derived glioblastoma cells was generated by implanting cells via intravitreal injection into the mouse eye [ 78 ]. This model allowed for the generation of tumours after approximately just 2 weeks, which consistently progressed to definitive masses by 4 weeks.…”

“…This PDX model allows for drug screens to begin just 6 weeks following the initial surgery and would allow for a fast turnaround time regarding potentially beneficial, additional treatments. The 6-week window required for generating these patient-specific PDX models is shorter than the average time between the patient’s initial surgery and tumour recurrence, thus this provides the potential to delay or even prevent recurrence of the disease [ 78 ].…”