The role of alpha 6 beta 1 integrin and EGF in normal and malignant acinarmorphogenesis of human prostatic epithelial cells

Complex multiple interactions between cells and extracellular matrix occur during acinar morphogenesis involving integrin receptors and growth factors , Changes in these interactions occur during carcinogenesis as cells progre ss from a normal to a malignant, invasive phenotype. We have developed huma n prostatic epithelial cell lines of the same lineage, which represent mult iple steps in carcinogenesis, similar to prostatic intraepithelial neoplasi a and subsequent tumor progression. The non-tumorigenic, RWPE-1 and the tum origenic WPE1-NB27 and WPE1-NB26 cell lines were used to examine their abil ity to undergo acinar morphogenesis in a 3-D cell culture model and its rel ationship to invasion, integrin expression and EGF presence. An inverse rel ationship between the degree of acinar formation and invasive ability was o bserved. The non-tumorigenic, non-invasive RWPE-1 and the low tumorigenic, low invasive, WPE1-NB27 cells show high and decreased acinar forming abilit y, respectively, while the more invasive WPE1-NB26 cells show a loss of aci nar formation. While RWPE-1 acini show basal expression of alpha6 beta1 int egrin, which correlates with their ability to polarize and form acini, WPE1 -NB27 cells lack alpha6 but show basal, but weaker expression of beta1 inte grin. beta1 WPE1-NB26 cells show loss alpha6 and abnormal, diffused beta1 i ntegrin expression. A dose-dependent decrease in acinar formation was obser ved in RWPE-1 cells when cell proliferation was induced by EGF. Anti-functi onal antibody to EGF caused an increase in acinar formation in RWPE-1 cells . These results suggest that malignant cells lose the ability to undergo ac inar morphogenesis and that the degree of this loss appears to be related t o invasive ability, EGF levels and alterations in laminin-specific integrin expression. This model system mimics different steps in prostate carcinoge nesis and has applications in the secondary and tertiary prevention of pros tate cancer. (C) 2001 Elsevier Science B.V. All rights reserved.