Characterization of a novel transplantable orthotopic rat bladder transitional cell tumour model

An animal tumour model that mimics the human counterpart is essential for p reclinical evaluation of new treatment modalities. The objective of this st udy was to develop and characterize such a model. To accomplish this, the e stablished AY-27 rat bladder transitional cell carcinoma (TCC) cell line wa s transplanted orthotopically into Fischer CDF344 female rats, AY-27 TCC ce lls were grown in monolayer cell culture and instilled intravesically as si ngle cell suspensions into bladders that had been conditioned with mild aci d washing. Tumour growth was assessed weekly by subjecting the rats to magn etic resonance imaging (MRI). At intervals following implantation and MRI t umour detection, the animals were sacrificed for necropsy, histological exa mination and immunocytochemical studies, Flow cytometry was also performed for detection of Fas or Fas-ligand expression on AY-27 cells. The overall t umour establishment was 95% (97/102 rats) at 12-50 days, while in a subgrou p of animals sacrificed at 16 days, 80 out of 82 animals (97%) developed TC C, the majority of which was superficial. Tumour stage was assessed by gros s pathology and light microscopy. Histological examination of the tumour sp ecimens confirmed the presence of grade II-III TCC. Immunocytochemistry con firmed that the tumour model maintained the features of TCC, The changes se en on MRI correlated well with the extent of tumour invasion identified his tologically. Patchy carcinoma in situ could be detected histologically 12-1 3 days post-inoculation, and progressed to papillary tumour or invasive dis ease thereafter. Neither Fas nor Fas-ligand was expressed on AY-27 cells. T he orthotopic AY-27 TCC model is highly reproducible and is ideal for precl inical studies on experimental intravesical therapies, (C) 1999 Cancer Rese arch Campaign.