EXPRESSION OF THE VLA BETA-1 INTEGRIN FAMILY IN BLADDER-CANCER

Integrins are a family of transmembrane heterodimers, many of which fu nction as receptors for extracellular matrix molecules and play a role in adherence to and motility on matrix components. Because of these f unctions, integrins are suspected of participating in metastatic proce sses. We investigated the expression of beta 1 integrins in human blad der cancer cell lines and tissues. Expression of beta 1 integrins on c ultured bladder cancer cell lines was evaluated by flow cytometry, of 8 cell lines tested, alpha 1 was found in 4, alpha 2 and alpha 3 in al l 8, alpha 4 in 1, and alpha 5 in 3. These results were in sharp contr ast to the expression detected by immunostaining tissues containing no rmal urothelium and low stage (noninvasive) and high stage (invasive) bladder cancers. All normal urothelial tissues tested expressed alpha 2 and alpha 3 and none expressed alpha 1, alpha 4, or alpha 5. Similar ly, a majority (77%) of low stage (noninvasive) bladder cancers staine d positively for alpha 3, whereas only 6 of 13 expressed alpha 2 and n one expressed alpha 1, alpha 4, or alpha 5. Among invasive bladder can cers, alpha 1 was detected in 7%, alpha 2 in 24%, alpha 3 in 68%, alph a 5 in 10%, and alpha 4 was not found in any samples. These results in dicate that integrin expression in cultured human bladder cancer cell lines does not represent expression observed in tissue samples and may reflect adaption to or selection during tissue culture conditions. A progressive loss of alpha 2 expression is seen from normal urothelial cells through invasive bladder cancers. This loss may contribute to an invasive phenotype by a loss of the cell-cell adherence function medi ated by the alpha 2 beta 1 and alpha 3 beta 1 integrins.