PUBLICATION

Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model

Authors
Marques, I.J., Weiss, F.U., Vlecken, D.H., Nitsche, C., Bakkers, J., Lagendijk, A., Partecke, L.I., Heidecke, C.D., Lerch, M.M., and Bagowski, C.P.
ID
ZDB-PUB-090505-1
Date
2009
Source
BMC cancer   9: 128 (Journal)
Registered Authors
Bagowski, Christoph P., Bakkers, Jeroen
Keywords
none
MeSH Terms
  • Animals
  • Cell Movement/physiology
  • Disease Models, Animal*
  • Gastrointestinal Neoplasms/pathology
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Neoplasm Transplantation*
  • Neoplasms/pathology*
  • Pancreatic Neoplasms/pathology
  • Transplantation, Heterologous
  • Zebrafish/embryology*
PubMed
19400945 Full text @ BMC Cancer
Abstract
BACKGROUND: Aberrant regulation of cell migration drives progression of many diseases, including cancer cell invasion and metastasis formation. Analysis of tumour invasion and metastasis in living organisms to date is cumbersome and involves difficult and time consuming investigative techniques. For primary human tumours we establish here a simple, fast, sensitive and cost-effective in vivo model to analyse tumour invasion and metastatic behaviour. METHODS: We fluorescently labeled small explants from gastrointestinal human tumours and investigated their metastatic behaviour after transplantation into zebrafish embryos and larvae. The transparency of the zebrafish embryos allows to follow invasion, migration and micrometastasis formation in real-time. High resolution imaging was achieved through laser scanning confocal microscopy of live zebrafish. RESULTS: In the transparent zebrafish embryos invasion, circulation of tumour cells in blood vessels, migration and micrometastasis formation can be followed in real-time. Xenografts of primary human tumours showed invasiveness and micrometastasis formation within 24 hours after transplantation, which was absent when non-tumour tissue was implanted. Furthermore, primary human tumour cells, when organotopically implanted in the zebrafish liver, demonstrated invasiveness and metastatic behaviour, whereas primary control cells remained in the liver. Pancreatic tumour cells showed no metastatic behaviour when injected into cloche mutant embryos, which lack a functional vasculature. CONCLUSIONS: Our results show that the zebrafish is a useful in vivo animal model for rapid analysis of invasion and metastatic behaviour of primary human tumour specimen.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping