Reduction of integrin β4 and enhanced migration on laminin in association with intraepithelial spreading of urinary bladder carcinomas

Tohru Harabayashi, Yae Kanai, Tesshi Yamada, Michiie Sakamoto, Atsushi Ochiai, Tadao Kakizoe, Tomohiko Koyanagi, Setsuo Hirohashi

Research output: Contribution to journalArticle

12 Citations (Scopus)


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 β4 subunit was markedly reduced and the integrin α6β1 complex was predominant compared with the integrin α6β4 complex. Transfection of IES cells with integrin β4 subunit cDNA inhibited their ability to migrate on laminin and their propensity for IES. In addition, expression of the integrin β4 subunit was reduced in surgically resected specimens of CIS of the urinary bladder. Conclusion: The results indicate that a reduction in integrin β4 plays a role in IES of CIS of the urinary bladder through enhanced migration on laminin.

Original languageEnglish
Pages (from-to)1364-1371
Number of pages8
JournalJournal of Urology
Issue number4
Publication statusPublished - 1999 Apr
Externally publishedYes



  • Carcmoma in situ
  • Integrin β
  • Intraepithelial spreading
  • Laminin
  • Urinary bladder carcinoma

ASJC Scopus subject areas

  • Urology

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