Background: More than 70% of muscle invasive bladder cancers (MIBC) express the cell-surface antigen sialyl-Tn (sTn) that promotes motility and invasive potential of tumor cells. Effective drug testing models to optimize therapy against these tumors are warranted.
Materials and methods: Fragments of sTn-positive MIBC were subcutaneously engrafted into nude mice and expanded until the third passage. Histology and immunoexpression of tumor markers (p53, p63, Ki-67, CK20, sTn) were studied in order to evaluate tumor phenotype maintenance.
Results: Tumor take rate was low in the first passage (1/9) but increased and became consistent, therefore suitable for drug testing, in the third passage (13/13). Histology and immunoexpression patterns were similar between primary tumors and xenografts. However, p53 and ki-67 levels increased with passages suggesting a selection of more proliferative clones. STn expression, even though decreased, was preserved in xenografts.
Conclusion: We describe the first patient-derived sTn-positive xenograft model to be used for drug testing and identification of prognostic biomarkers.
Keywords: Human xenografts; animal models; drug testing; glycosylation; sialyl-Tn; urothelial cancer.