학술논문

Development of a Simple and Reproducible Cell-derived Orthotopic Xenograft Murine Model for Neuroblastoma.
Document Type
article
Source
In Vivo. 38(2)
Subject
Neuroblastoma
PDOX
orthotopic murine model
Child
Humans
Animals
Mice
Disease Models
Animal
Heterografts
Mice
SCID
Neuroblastoma
Adrenal Gland Neoplasms
Xenograft Model Antitumor Assays
Cell Line
Tumor
Language
Abstract
BACKGROUND/AIM: Neuroblastoma is a common childhood cancer with poor survival for children with high-risk disease, and ongoing research to improve outcomes is needed. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are reliable models for oncologic research; however, they are resource-intensive, expensive, and require significant expertise to develop and maintain. We developed an orthotopic xenograft murine model of neuroblastoma that utilizes cryopreserved banks of human neuroblastoma cell lines, requires minimal equipment, and is easily reproducible. MATERIALS AND METHODS: The neuroblastoma cell line NB1643 was obtained from the Childrens Oncology Group (COG) Childhood Cancer Repository. Nod-SCID-gamma (NSG) mice underwent orthotopic injection of 2x106 NB1643 cells suspended in 10 μl of collagen hydrogel directly into the adrenal gland via an open retroperitoneal surgical approach. Mice were monitored by ultrasound and in vivo imaging system (IVIS) until the tumor reached the volume of the ipsilateral kidney. Tumor identity was confirmed by necropsy and histologic analysis. RESULTS: A total of 55 mice underwent surgery. Eight died due to anesthetic or surgical complications. 39/47 (78%) survivors grew primary adrenal tumors. Average anesthesia time was 30 min. Ultrasound and IVIS successfully characterized tumor growth in all mice. Average time to target tumor size was 5 weeks (range=3-9). Gross pathologic and histologic analysis confirmed adrenal tumors consistent with neuroblastoma in all mice with adrenal masses. CONCLUSION: A cell-derived orthotopic xenograft murine model can be successfully used to create an in vivo model of neuroblastoma. This model can be utilized in environments where PDX or GEMM models are not feasible.