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Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model

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...

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Autores principales: Chen, Xiaoyun, Wang, Jian, Cao, Ziquan, Hosaka, Kayoko, Jensen, Lasse, Yang, Huasheng, Sun, Yuping, Zhuang, Rujie, Liu, Yizhi, Cao, Yihai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501005/
https://www.ncbi.nlm.nih.gov/pubmed/26169357
http://dx.doi.org/10.1038/srep10351
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author Chen, Xiaoyun
Wang, Jian
Cao, Ziquan
Hosaka, Kayoko
Jensen, Lasse
Yang, Huasheng
Sun, Yuping
Zhuang, Rujie
Liu, Yizhi
Cao, Yihai
author_facet Chen, Xiaoyun
Wang, Jian
Cao, Ziquan
Hosaka, Kayoko
Jensen, Lasse
Yang, Huasheng
Sun, Yuping
Zhuang, Rujie
Liu, Yizhi
Cao, Yihai
author_sort Chen, Xiaoyun
collection PubMed
description 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.
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spelling pubmed-45010052015-07-17 Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model Chen, Xiaoyun Wang, Jian Cao, Ziquan Hosaka, Kayoko Jensen, Lasse Yang, Huasheng Sun, Yuping Zhuang, Rujie Liu, Yizhi Cao, Yihai Sci Rep Article 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. Nature Publishing Group 2015-07-14 /pmc/articles/PMC4501005/ /pubmed/26169357 http://dx.doi.org/10.1038/srep10351 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chen, Xiaoyun
Wang, Jian
Cao, Ziquan
Hosaka, Kayoko
Jensen, Lasse
Yang, Huasheng
Sun, Yuping
Zhuang, Rujie
Liu, Yizhi
Cao, Yihai
Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model
title Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model
title_full Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model
title_fullStr Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model
title_full_unstemmed Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model
title_short Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model
title_sort invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501005/
https://www.ncbi.nlm.nih.gov/pubmed/26169357
http://dx.doi.org/10.1038/srep10351
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