Hypoxia-induced metastasis model in embryonic zebrafish

Pegah Rouhi, Lasse D. Jensen, Ziquan Cao, Kayoko Hosaka, Toste Lanne, Eric Wahlberg, John Fleng Steffensen, Yihai Cao

83 Citations (Scopus)

Abstract

Hypoxia facilitates tumor invasion and metastasis by promoting neovascularization and co-option of tumor cells in the peritumoral vasculature, leading to dissemination of tumor cells into the circulation. However, until recently, animal models and imaging technology did not enable monitoring of the early events of tumor cell invasion and dissemination in living animals. We recently developed a zebrafish metastasis model to dissect the detailed events of hypoxia-induced tumor cell invasion and metastasis in association with angiogenesis at the single-cell level. In this model, fluorescent DiI-labeled human or mouse tumor cells are implanted into the perivitelline cavity of 48-h-old zebrafish embryos, which are subsequently placed in hypoxic water for 3 d. Tumor cell invasion, metastasis and pathological angiogenesis are detected under fluorescent microscopy in the living fish. The average experimental time for this model is 7 d. Our protocol offers a remarkable opportunity to study molecular mechanisms of hypoxia-induced cancer metastasis.
Original languageEnglish
JournalNature Protocols (Print)
Volume5
Issue number12
Pages (from-to)1911-1918
Number of pages8
ISSN1754-2189
DOIs
Publication statusPublished - Nov 2010

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