Isolation and characterization of invasive and noninvasive variants of a rat bladder tumor cell line

We isolated, in vitro, spontaneous variants of the rat bladder tumor NBT-II cell line with a distinctive morphology. Of five sublines obtained, three (NBT-L1, L2a and L2b) exhibited an elongated shape and moderate to high invasive activity in vitro. The other two sublines (NBT-T1 and T2) formed tight colonies and exhibited very low or negligible invasive activity. The contents of mRNAs coding for E-cadherin and cadherin-associated molecules (alpha-catenin and beta-catenin) were not correlated with the invasive activity of the cells. However, the expression level of the E-cadherin protein, but not those of catenins, was lower in invasive cells (NBT-L1, L2a and L2b) than in noninvasive cells (NBT-T1 and T2). Analysis of mRNAs coding for several growth factors and their receptors showed that the transforming growth factor alpha mRNA content in invasive cells was higher than that in noninvasive cells, and that the content of epidermal growth factor receptor mRNA was low in NBT-T2. Although NBT-II is known to acquire a fibroblastic appearance and cell motility in response to several growth factors, the conditioned media of the invasive sublines hardly affected the morphology or motility of noninvasive cells. These results indicate that the decreased E-cadherin expression is closely associated with the transition from the noninvasive to the invasive phenotype of the bladder tumor cells, and that a post-transcriptional process is important in the control of E-cadherin expression in the cells. These sublines may be useful as models for studies on the progression of bladder tumors.