Reduction of integrin beta 4 and enhanced migration on laminin in association with intraepithelial spreading of urinairy bladder carcinomas

Purpose: The aim of the present study was to investigate the biological and molecular basis of intraepithelial spreading (IES) of carcinomas in situ ( CIS) of the urinary bladder, which were considered to be precursors of nodu lar invasive carcinomas. Materials and Methods: The propensity for IES of human transitional carcino ma cells was examined by inoculation into murine renal. pelvis and urinary bladder, and the biological character of the cells with a high propensity f or IES was explored in vitro. Results: Three of 6 cell lines exhibited a high propensity for IES. When cu ltured on laminin, these IES cells scattered, whereas 3 non-IES cells and 2 immortalized transitional epithelial cells did not. IES cells showed stron g adhesiveness, haptotaxis and enhanced migration on laminin compared with both non-IES and immortalized transitional epithelial cells. In IES cells, expression of the integrin beta(4) subunit was markedly reduced and the int egrin alpha(6)beta(1) complex was predominant compared with the integrin al pha(6)beta 74 complex. Transfection of IES cells with integrin beta(4) subu nit cDNA inhibited their ability to migrate on laminin and their propensity for IES. In addition, expression of the integrin beta(4) subunit was reduc ed in surgically resected specimens of CIS of the urinary bladder. Conclusion: The results indicate that a reduction in integrin beta(4) plays a role in IES of CIS of the urinary bladder through enhanced migration on laminin.