Novel invasive orthotopic bladder cancer model with high catepsin B activity resembling human bladder cancer disease

CATALINA LODILLINSKY; VANINA RODRIGUEZ; LILIANA VAUTHAY; EDUARDO SANDES; ALBERTO CASABÉ; ANA MARIA EIJAN

JOURNAL OF UROLOGY

Elsevier

Lugar: Official Journal of the American Urological Association; Año: 2009 vol. 182 p. 1749 - 1755

0022-5347

Purpose: The aim of this work was development and characterization of an orthotopic invasive bladder tumor model. Material methods and results: The MB49-I tumor cell line was obtained after thirteen consecutive in vivo passages of primary tumor obtained by subcutaneous (sc) inoculation of MB49 bladder tumor cells in C57Bl/6 male mice. Local invasiveness, tumor weight and spontaneous metastatic capacity of MB49-I tumors was higher than those of MB49 ones. In the MB49-I bladder tumor an increase in vimentin (VM) was observed suggesting epithelial mesenchymal transition. In vitro, MB49-I cell line showed higher invasive properties, associated with an increase in the proteolytic activities of Cathepsin B, Metalloproteinase 9, and urokinase-type plasminogen activator. Orthotopic bladder tumors induced by electrocautery of the bladder wall and subsequent instillation of MB49 and MB49-I bladder cancer cells generate superficial and invasive bladder tumor respectively. Conclusions: The new murine bladder model described here resembles bladder human disease, thus making it a very useful tool both to study the molecular mechanisms involved in tumor progression and metastases, and to assay anti metastatic and anti invasive agents.