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

• Published in: Experimental & molecular medicine Vol. 51; no. 4; pp. 1 - 9
• Main Authors: Lee, Jooyoung, Jo, Dong Hyun, Kim, Jin Hyoung, Cho, Chang Sik, Han, Jiwon Esther, Kim, Yona, Park, Hyoungwoo, Yoo, Seung Ho, Yu, Young Suk, Moon, Hyo Eun, Park, Hye Ran, Kim, Dong Gyu, Kim, Jeong Hun, Paek, Sun Ha
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.04.2019; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 13/1; 14/19; 631/67/1922; 64/60; 692/699/67/1922; 82/51; Adult; Animal models; Animals; Biomedical and Life Sciences; Biomedicine; Brain cancer; Brain tumors; Cell Line, Tumor; Disease Models, Animal; Female; Fluorescent Antibody Technique; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - analysis; Glioblastoma; Glioblastoma - pathology; Glioblastoma cells; Humans; Immunohistochemistry; Injection; Intravitreal Injections - methods; Male; Medical Biochemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Mimicry; Mitochondria; Mitochondria - metabolism; Molecular Medicine; Nestin; Parenchyma; Patients; Plaques; Stem Cells; Tumor cells; Tumor Cells, Cultured; Tumors; Vimentin; Vimentin - analysis; Xenograft Model Antitumor Assays; Xenografts; 생화학
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.1038/s12276-019-0241-3

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. Brain cancer: A clearer view of glioblastoma An improved strategy for cultivating patient-derived tumors in mice gives researchers a faster, more accurate means for testing glioblastoma treatments. Such ‘xenograft’ models are powerful tools for characterizing a patient’s cancer, but current cultivation techniques are too slow or fail to capture key features of this deadly disease. Researchers led by Jeong Hun Kim and Sun Ha Paek at Seoul National University Hospital in South Korea have demonstrated that glioblastoma cells injected into the mouse eye produce growths that mirror key characteristics of the original tumor. The tissue environment of the retina is physiologically similar to that of the brain, and cancer cells injected into the eye form glioblastoma-like tumors twice as quickly as the same cells injected into the skull. This means clinical researchers can assess drug response and accordingly adjust patient care more quickly.