Whole-body bioluminescent Imaging of human uveal melanoma in a new mouse model of local tumor growth and metastasis
Whole-body bioluminescent Imaging of human uveal melanoma in a new mouse model of local tumor growth and metastasis
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DOI：
10.1167/iovs.04-0245
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
van der Pluijm, G
中科院分区：
文献类型：
--
作者：
Notting, IC;Buijs, JT;van der Pluijm, G
目的.人葡萄膜黑色素瘤发生于人体毛细血管最丰富的组织之一，并具有纯血行播散。放射诊断检查，如超声诊断共振成像和胸部X光片加上血液中的肝酶研究，是用于检测患者肝脏和其他远处转移的方法。然而，由于经常发生转移和缺乏系统治疗，死亡率很高。因此，迫切需要开发新的抗癌策略，并需要更灵敏和侵入性更小的方法来检测和监测体内肿瘤生长和癌症模型中的转移性疾病。建立了荧光素酶（Luc）阳性的人葡萄膜黑色素瘤细胞系（OCM-1 FRT/luc）。将肿瘤细胞接种到小鼠眼睛的前房中以诱导原位生长或接种到左心室中以模拟血行性微转移扩散。每周通过全身生物发光报告成像（BLI）监测转移和肿瘤生长的发展。将癌细胞注射到小鼠眼前房中，非常接近葡萄膜黑色素瘤的原位肿瘤生长。在接种105个OCM-1 FRT/luc细胞后3周，可定量监测肿瘤进展。在注射的小鼠中，83%在5周内表现出可检测到的肿瘤。心内注射肿瘤细胞导致转移性生长，特别是在骨中。小鼠在4至6周后出现骨（颌面部和股骨）和内脏（肺和纵隔）转移。OCM-1 FRT/luc细胞在心内接种后也可能具有在眼内定植的倾向。BLI能够在同一动物中连续定量监测每种肿瘤及其转移的生长动力学。这一模型将促进对葡萄膜黑色素瘤及其转移的发病机制和治疗的理解。
PURPOSE. Human uveal melanoma develops in one of the most capillary-rich tissues of the body and has a pure hematogenous dissemination. Radiodiagnostic examinations, such as ultrasonic diagnostic resonance imaging and chest radiographs plus liver enzyme studies in blood, are methods used to detect liver and other distant metastases in patients. Nevertheless, the mortality rate is high, because of the frequent occurrence of metastases and the lack of systemic therapy. Therefore, the development of novel anticancer strategies is urgent, and more sensitive and less invasive methods of detecting and monitoring in vivo tumor growth and metastatic disease in cancer models are needed.METHODS. A luciferase (Luc)-positive human uveal melanoma cell line (OCM-1 FRT/luc) was established. Tumor cells were inoculated into the anterior chamber of murine eyes for induction of orthotopic growth or into the left heart ventricle to mimic hematogenous micrometastatic spread. Development of metastases and tumor growth was monitored weekly by whole-body bioluminescent reporter imaging (BLI).RESULTS. Injection of cancer cells into the anterior chamber of the eye of mice closely mimicked orthotopic tumor growth of uveal melanoma. Tumor progression could be quantitatively monitored 3 weeks after inoculation of 105 OCM-1 FRT/luc cells. Of the mice injected, 83% exhibited a detectable tumor within 5 weeks. Intracardiac injection of tumor cells resulted in metastatic growth, especially in bone. Mice had bone ( maxillofacial region and femora) and visceral ( lung and mediastinum) metastases after 4 to 6 weeks. OCM-1 FRT/luc cells may also have a propensity to colonize the eye after intracardiac inoculation.CONCLUSIONS. BLI enables continuous quantitative monitoring in the same animal of growth kinetics for each tumor and its metastases. This model will accelerate the understanding of the pathogenesis and treatment of uveal melanoma and metastasis.