Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model.
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 labelled 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.
Marques
Ines J
IJ
Institute of Biology, Department of Integrative Zoology, University of Leiden, 2333 AL, Leiden, The Netherlands. i.j.marques@biology.leidenuniv.nl
Weiss
Frank Ulrich
FU
Vlecken
Danielle H
DH
Nitsche
Claudia
C
Bakkers
Jeroen
J
Lagendijk
Anne K
AK
Partecke
Lars Ivo
LI
Heidecke
Claus-Dieter
CD
Lerch
Markus M
MM
Bagowski
Christoph P
CP
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D004195:Disease Models, Animal; D005770:Gastrointestinal Neoplasms / Q000473:pathology; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000473:pathology; D014183:Transplantation, Heterologous; D015027:Zebrafish / Q000196:embryology*