Highly metastatic K7M2 cell line: A novel murine model capable of in vivo imaging via luciferase vector transfection
Highly metastatic K7M2 cell line: A novel murine model capable of in vivo imaging via luciferase vector transfection
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DOI：
10.1002/jor.23868
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发表时间：
2018-08-01
影响因子：
2.8
通讯作者：
Lindsey, Brock A.
中科院分区：
文献类型：
--
作者：
Grisez, Brian T.;Ray, Justin J.;Lindsey, Brock A.
骨肉瘤是罕见的，在过去的25年里，尽管有现代的化疗治疗，生存率几乎没有提高。用于骨肉瘤建模的生物发光细胞系在体内追踪转移方面已经显示出成功，但通常使用腺病毒载体转染具有生物发光报告细胞的天然细胞系。本研究的目的是建立转移性骨肉瘤的原位模型，能够在免疫功能正常的小鼠体内监测转移性和原发肿瘤负荷，并将该模型与野生型的发病机制进行比较。用质粒载体转染K7M2细胞，12周后细胞稳定。34只4-5周龄雌性BALB/c小鼠在胫骨近端原位植入野生型（n=12）或转染型（n=22） K7M2细胞。监测小鼠肿瘤生长情况，每周进行体内成像系统（IVIS）成像监测肺转移。尽管野生型组的肿瘤发展得更快，但与转染1组相比，在接种率、首次检测后的生长速度、转移率和接种至死亡的时间方面没有显著差异。本研究利用转染非病毒质粒荧光素酶载体的K7M2-wt细胞系建立了转移性骨肉瘤小鼠模型。这种临床前模型的好处包括完整的免疫系统和原位驱动的转移性疾病；这个模型看起来与它的野生型对应模型相当。在未来，该模型可用于研究有前途的免疫调节疗法使用生物发光在体内。(c) 2018年骨科研究会。Wiley期刊公司出版。[J]中华骨科杂志，2018。
Osteosarcoma is rare and little improvement in survival rates has occurred in the last 25 years despite modern chemotherapeutic treatment. Bioluminescent cell lines for the modeling of osteosarcoma have shown success in tracking metastases in vivo, but commonly use adenoviral vectors to transfect the native cell line with bioluminescent reporters. The purpose of this study was to develop an orthotopic model for metastatic osteosarcoma capable of in vivo monitoring of metastatic and primary tumor burden in an immunocompetent mouse and compare that model to its wild type pathogenesis. K7M2 cells were transfected using a plasmid vector and were stable after 12 weeks. Thirty-four female BALB/c mice aged 4-5 weeks underwent orthotopic implantation of either wild type (n=12) or transfected (n=22) K7M2 cells in the proximal tibia. Mice were monitored for tumor growth and weekly In Vivo Imaging System (IVIS) imaging was performed to monitor for pulmonary metastasis. Although tumors developed sooner in the wild type group, no significant differences were seen compared to Transfected Group 1 in rate of inoculation, growth rates after first detection, metastatic rate, and time between inoculation and death. This study establishes a new murine model for metastatic osteosarcoma using the K7M2-wt cell line transfected with a non-viral plasmid luciferase vector. The benefits of this preclinical model include an intact immune system and orthotopically driven metastatic disease; this model appears comparable to its wild type counterpart. In the future, the model may be used to examine promising immunomodulatory therapies using bioluminescence in vivo. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2296-2304, 2018.