A Metastasizing Model of Anaplastic Human Wilms Tumor in the Nude Mouse*

Abstract

Reproducible animal models of Wilms tumor have been difficult to establish. We describe a model in which cells, banked from a patient with metastatic Wilms tumor, were implanted into nude mice, resulting in the development of primary renal and metastatic pulmonary lesions. Pathologically, the lesions resembled the blastemal component of anaplastic Wilms tumor. Primary tumors showed a significant propensity for growth in the kidney as opposed to other organs. Pulmonary metastases, histologically similar to the primary lesions, were regularly observed. This represents the first reproducible model of anaplastic, metastasizing human Wilms tumor. This system may prove effective for the study of factors influencing growth and angiogenesis in aggressive variants of Wilms tumor.

Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies

“…An orthotopic nude mouse model was used to evaluate UAB30 upon the growth of renal Ewing sarcoma cells and their ability to form lung metastasis [20, 22]. SK-NEP-1 cells (1.5 × 10 6 ) were injected into the subcapsular space of the left kidney of female athymic nude mice (n = 28).…”

“…Ki67 staining was completed on these xenografts tumors, and again tended to be higher in the untreated tumors, but did not reach statistical significance. Since SK-NEP-1 tumors are known to metastasize to the lungs [20, 22], lung tissues were stained with H & E to detect metastases. A representative example of a pulmonary metastasis (40×) in a control treated animal is presented in Figure 5E.…”

“…When injected into the orthotopic position these cells will form lung metastasis [20, 22]. At injection, animals were randomized to daily administration of vehicle-treated or UAB30-treated (100 mg/kg body weight/day) chow (n = 10 per group).…”

Expression of cytokeratin‐18‐related tissue polypeptide‐specific (TPS) antigen in Wilms tumor

“…Possibly there is also a difference between in vitro and in vivo conditions. An animal model using the SK-NEP-1 cell line has recently been established [37] and could be used to further clarify this issue. It has been shown that rapid hyperphosphorylation of K18 intermediate ®laments is followed by proteolytic fragmentation and constitutes an early indicator of apoptosis.…”

Wilms tumor: progress to date and future considerations

“…New protocols and investigations will further clarify current genetic markers and define whether these markers are associated with tumor aggressiveness or response to therapy. In vivo molecular models that elucidate critical determinants of tumor growth, metastasis and angiogenesis will be further refined [50]. Finally, therapies based on restoring normal biological gene function will be developed and included in the treatment of children with WT [51].…”