The epithelial mesenchymal transition process in wilms tumor: a study based on a xenograft model.

BACKGROUND

Until now, only a few mouse-transplanted human tumors or experimental Wilms tumor (WT) cell lines have been described. The aim of this study was to show the biological behavior, including histology, immunohistochemistry (IHC), and molecular biology, of a WT including the original tumor and metastasis transferred into nude mice and followed for successive generations in xenografts.

METHODS

A WT metastasis was xenotransplanted into nude mice and the mice was monitored for 7 passages over a period of 29 months; the original neoplasm was comparatively studied. The morphology was evaluated by optical and electron microscopy. The protein expression was analyzed by immunohistochemistry in whole sections and in tissue microarray. The molecular studies were carried out by multiplex ligation-dependent probe amplification and polymerase chain reaction analysis.

RESULTS

The histology changed markedly between the fourth and fifth transfer. The tumor exhibited an increased epithelial component (>40%) together with a slowing in the growth rate (8 mo). An epithelial-mesenchymal transition seemed to take place in the fourth passage and increased thereafter. The genetic studies also showed a WT5 deletion and a MYCN gain in all the tumor samples in passage 4 and beyond, but did not show E-cadherin, β-catenin, and APC mutations.

CONCLUSIONS

An epithelial pattern was associated with slow tumor growth, whereas the predominance of mesenchymal spindle cells with striated muscle cell differentiation was related with a high growth rate. The in vivo reorganization of the tumor components (blastemal, epithelial, and mesenchymal) does not seem to be related with the Wnt and EMT pathways.