title: Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model.
abstract: Retinoblastoma is a highly invasive malignant tumor that often invades the brain and metastasizes to distal organs through the blood stream. Invasiveness and metastasis of retinoblastoma can occur at the early stage of tumor development. However, an optimal preclinical model to study retinoblastoma invasiveness and metastasis in relation to drug treatment has not been developed. Here, we developed an orthotopic zebrafish model in which retinoblastoma invasion and metastasis can be monitored at a single cell level. We took the advantages of immune privilege and transparent nature of developing zebrafish embryos. Intravitreal implantation of color-coded retinoblastoma cells allowed us to kinetically monitor tumor cell invasion and metastasis. Further, interactions between retinoblastoma cells and surrounding microvasculatures were studied using a transgenic zebrafish that exhibited green fluorescent signals in blood vessels. We discovered that tumor cells invaded neighboring tissues and blood stream when primary tumors were at the microscopic sizes. These findings demonstrate that retinoblastoma metastasis occurs at the early stage and antiangiogenic drugs such as Vegf morpholino and sunitinib could potentially interfere with tumor invasiveness and metastasis. Thus, this orthotopic retinoblastoma model offers a new and unique opportunity to study the early events of tumor invasion, metastasis and drug responses.
authors.affiliation: 1] The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guanzhou, 510060, People's Republic of China [2] Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Chen
authors.affiliation: 1] Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden [2] Department of Oncology, Jinan Central Hospital, Shandong University, NO.105, Jiefang Road, Jinan, Shandong 250013, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1] Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden [2] Department of Medicine and Health Sciences, Linköping University, 581 83. Linköping, Sweden.
authors.forename: Ziquan
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Hosaka
authors.affiliation: 1] Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden [2] Department of Medicine and Health Sciences, Linköping University, 581 83. Linköping, Sweden.
authors.forename: Lasse
authors.initials: L
authors.lastname: Jensen
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guanzhou, 510060, People's Republic of China.
authors.forename: Huasheng
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, NO.105, Jiefang Road, Jinan, Shandong 250013, People's Republic of China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Zhejiang First affiliated Hospital of Chinese Medical University, Hangzhou, 310006, People´s Republic of China.
authors.forename: Rujie
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guanzhou, 510060, People's Republic of China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1] Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden [2] Department of Medicine and Health Sciences, Linköping University, 581 83. Linköping, Sweden [3] Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, LE3 9QP, UK.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D060172:Morpholinos / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011758:Pyrroles / Q000494:pharmacology; D012175:Retinoblastoma / Q000188:drug therapy / Q000473:pathology*; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D015027:Zebrafish
chemical_list: D007211:Indoles; D060172:Morpholinos; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib