Isolation and Characterization of Metastatic Variants from Human Transitional Cell Carcinoma Passaged by Orthotopic Implantation in Athymic Nude Mice

Abstract

This reproducible model of human bladder cancer offers the opportunity to study cellular properties associated with tumor progression and metastasis and is suitable for the evaluation of new therapeutic strategies for invasive bladder cancer.

Tumor Progression of Skin Carcinoma Cells in Vivo Promoted by Clonal Selection, Mutagenesis, and Autocrine Growth Regulation by Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor

“…Thus, these cell lines confirmed a stable tumor progression from benign to highly malignant and metastatic cells in the in vivo environment. The selection of a more malignant phenotype in vivo has also been reported for other tumor systems such as prostate carcinomas, 49 colon carcinomas, 50 transitional cell carcinomas of the bladder, 51 and pancreatic carcinomas. 52,53 In these studies, in vivo passage of tumor cells resulted in increasingly malignant tumor cell populations with a higher metastatic potential than exhibited by the parental cell lines.…”

“…A-5RT cells induce an earlier and stronger activation of the tumor stroma and an enhanced angiogenic response, partly resulting from strong vascular endothelial growth factor expression (S Vosseler, M Skobe, and NE Fusenig, unpublished observations). In vivo selection of more malignant tumor cell populations with a higher metastatic potential has also been reported for prostate carcinomas, 49 colon carcinomas, 50 transitional cell carcinomas of the bladder, 51 and pancreatic carcinomas. 52,53 Tumor progression in these systems is also associated with the increased expression of angiogenic growth factors such as vascular endothelial growth factor and basic fibroblast growth factor and other cytokines such as interleukin-8.…”

In vivo upregulation of CD95 and CD95L causes synergistic inhibition of angiogenesis by TSP1 peptide and metronomic doxorubicin treatment

“…26 Animals that received DI-TSP/DXR combination treatment showed a significant delay in tumor onset compared to the single treatments and to the control vehicle. This delay was followed by tumor stabilization (Figure 4a).…”

The use of the orthotopic model to validate antivascular therapies for cancer

“…The importance of the orthotopic environment for reproducing human tumour conditions has been indeed shown for colon (Thalheimer, 2006), renal (Naito, 1987), breast (Price, 1990), bladder (Dinney, 1995), prostate (Stephenson, 1992), pancreatic (Bruns, 1999), lung (Boehle, 2000), esophageal (Gros, 2009) carcinomas and in neuroectoderma-derived tumours, such as melanoma and neuroblastoma (Pastorino, 2003a;Pastorino, 2007).…”