TY - JOUR
T1 - Reduction of integrin β4 and enhanced migration on laminin in association with intraepithelial spreading of urinary bladder carcinomas
AU - Harabayashi, Tohru
AU - Kanai, Yae
AU - Yamada, Tesshi
AU - Sakamoto, Michiie
AU - Ochiai, Atsushi
AU - Kakizoe, Tadao
AU - Koyanagi, Tomohiko
AU - Hirohashi, Setsuo
PY - 1999/4
Y1 - 1999/4
N2 - 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.
AB - 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.
KW - Carcmoma in situ
KW - Integrin β
KW - Intraepithelial spreading
KW - Laminin
KW - Urinary bladder carcinoma
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U2 - 10.1016/S0022-5347(01)61685-9
DO - 10.1016/S0022-5347(01)61685-9
M3 - Article
C2 - 10081909
AN - SCOPUS:0032588093
VL - 161
SP - 1364
EP - 1371
JO - Investigative Urology
JF - Investigative Urology
SN - 0022-5347
IS - 4
ER -