Bladder Cancer Studies Using In Vitro Models

Expression profiling using bladder cancer cell lines has been used to gain insight into the molecular events associated with clinical disease states, assigning potential functional roles to novel genes in both tumorigenic and tumor progression processes. Certain studies have focused on gene and pathway discovery associated to genistein[10] or 5-aza-2'-deoxycytidine[11] exposure. Other reports describe the functional classification of genes comparing the expression patterns of p53-mediated apoptosis in resistant tumor cell lines versus sensitive tumor cell lines using cDNA arrays,[12] or the expression patterns of a metastatic variant cell line to the respective parental invasive cells.[13] Many molecular targets involved in bladder cancer progression have been identified in these studies. Comprehensive analyses using clinical specimens will also elucidate the clinical utility of these targets as biomarkers for patients with bladder cancer. An attempt to tumor subtypes classification of bladder cancer cell lines by means of gene expression analyses has rendered identification of biomarkers of clinical utility. Gene profiling identified novel biomarkers from in vitro analyses that were proven to be associated with clinical and histopathological variables when validated on tumor specimens using tissue microarrays at the protein level, using well-characterized antibodies and immunohisto-chemistry. Caveolin-1 and keratin 10 were differentially expressed in a squamous carcinoma cell line and certain invasive tumor cell lines. Cells clustered also based on their p53, RB, and INK4A status revealing E-cadherin, zyxin, and moesin as targets differentially expressed in these clusters. The expression of all these proteins in primary bladder tumors spotted on tissue microarrays was significantly associated with histopathological stage and tumor grade.[14]

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