EXPRESSION OF INTEGRIN SUBUNITS IN NORMAL AND MALIGNANT HUMAN SALIVARY-GLAND CELL CLONES AND ITS REGULATION BY TRANSFORMING GROWTH-FACTOR-BETA-1

In this study, we have examined the expression of integrin subunits in normal and malignant human salivary gland cell clones as well as its regulation by transforming growth factor-beta 1 (TGF-beta 1). By the a nalysis using immunofluorescence staining, an SV40 immortalized normal human salivary gland duct cell clone (NS-SVDC) with no tumorigenic ab ility by s.c. implantation into nude mice was identified to express th e integrin beta 1, alpha 2, alpha 3 and alpha 6 subunits on the cell s urface, while the expression of these subunits, except for beta 1 subu nit, was reduced or completely diminished in a neoplastic human saliva ry gland duct cell clone (HSGc) with tumorigenic but not metastatic po tential in nude mice and metastatic cell clones derived after in vitro exposure of HSGc to N-methyl-N-nitrosourea. in addition, immunoblot a nalysis also exhibited the same results as those obtained with immunof luorescence staining. The alpha 1 subunit was not demonstrable in any of the cell clones by both techniques. TGF-beta 1 augmented the expres sion of the beta 1 subunit in NS-SV-DC, while HSGc and metastatic cell clones demonstrated no changes in the expression of the beta 1 subuni t in response to TGF-beta 1. These findings, therefore, suggest that t here is an inverse relationship between the malignancy and the express ion mode of integrin subunits, especially alpha 2 subunit, in human sa livary gland cell clones with varying degrees of malignant potential, and that TGF-beta 1 is a positive regulatory factor in the expression of the beta 1 subunit in normal but not malignant cell clones.