Reduction of integrin beta4 and enhanced migration on laminin in association with intraepithelial spreading of urinary 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 nodular invasive carcinomas.

MATERIALS AND

METHODS

The propensity for IES of human transitional carcinoma cells was examined by inoculation into murine renal pelvis and urinary bladder, and the biological character of the cells with a high propensity for IES was explored in vitro.

RESULTS

Three of 6 cell lines exhibited a high propensity for IES. When cultured on laminin, these IES cells scattered, whereas 3 non-IES cells and 2 immortalized transitional epithelial cells did not. IES cells showed strong adhesiveness, haptotaxis and enhanced migration on laminin compared with both non-IES and immortalized transitional epithelial cells. In IES cells, expression of the integrin beta4 subunit was markedly reduced and the integrin alpha6beta1 complex was predominant compared with the integrin alpha6beta4 complex. Transfection of IES cells with integrin beta4 subunit cDNA inhibited their ability to migrate on laminin and their propensity for IES. In addition, expression of the integrin beta4 subunit was reduced in surgically resected specimens of CIS of the urinary bladder.

CONCLUSION

The results indicate that a reduction in integrin beta4 plays a role in IES of CIS of the urinary bladder through enhanced migration on laminin.