Noninvasive visualization of retinoblastoma growth and metastasis via bioluminescence imaging.
OBJECTIVE
To establish human retinoblastoma (RB) animal models that allow sensitive, noninvasive and continuous monitoring of tumor growth and metastasis in vivo.


METHODS
The human RB tumor cell lines HXO-Rb44 and Y79 were engineered to express a fusion reporter gene allowing for bioluminescence and fluorescence imaging. Intraocular and metastatic tumors were induced in immunodeficient nude mice by injection of bioluminescent RB cells into eye compartments and into the left ventricle or tail vein. The growth kinetics of intraocular and metastatic tumors was quantitatively and continuously monitored via bioluminescence imaging (BLI).


RESULTS
Intraocular injection of HXO-Rb44-GFP-luc cells resulted in 100%, 80%, and 80% successful RB tumor development in the anterior chamber, vitreal cavity and subretinal space, respectively. The subretinal injection of Y79-GFP-luc cells resulted in 100% tumor development. BLI signal intensity correlated with the number of tumor cells injected as well as the weight of the tumor-bearing eyes. After bilateral subretinal injection of HXO-Rb44-GFP-luc cells, one of six RB tumor mice developed brain metastasis. Intracardiac injection of HXO-Rb44-GFP-luc cells resulted in metastatic disease in 9 of 15 nude mice, whereas tail vein injection resulted in metastasis in 1 of 16. Metastases were developed in multiple organs, including lymph nodes, bone, and brain, resembling the metastatic profile in patients with RB.


CONCLUSIONS
BLI allowed sensitive, noninvasive, and quantitative localization and monitoring of intraocular and metastatic RB tumor growth in vivo and thus may be a useful tool to study RB biology as well as anti-RB therapies.
Ji
Xunda
X
Experimental Center, The First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Cheng
Lin
L
Wei
Fang
F
Li
Huiming
H
Wang
Mengyun
M
Tian
Yuhua
Y
Chen
Xiafang
X
Wang
Yufei
Y
Wolf
Frank
F
Li
Chuanyuan
C
Huang
Qian
Q
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary*; D001932:Brain Neoplasms / Q000235:genetics / Q000556:secondary*; D002675:Child, Preschool; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008163:Luminescent Measurements; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000235:genetics; D019572:Retinal Neoplasms / Q000235:genetics / Q000473:pathology*; D012175:Retinoblastoma / Q000235:genetics / Q000556:secondary*; D014162:Transfection; D014407:Tumor Cells, Cultured
D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D008156:Luciferases