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 analysis using immunofluorescence staining, an SV40 immortalized normal human salivary gland duct cell clone (NS-SVDC) with no tumorigenic ability by s.c. implantation into nude mice was identified to express the integrin beta 1, alpha 2, alpha 3 and alpha 6 subunits on the cell surface, while the expression of these subunits, except for beta 1 subunit, was reduced or completely diminished in a neoplastic human salivary gland duct cell clone (HSGc) with tumorigenic but not metastatic potential in nude mice and metastatic cell clones derived after in vitro exposure of HSGc to N-methyl-N-nitrosourea. In addition, immunoblot analysis also exhibited the same results as those obtained with immunofluorescence staining. The alpha 1 subunit was not demonstrable in any of the cell clones by both techniques. TGF-beta 1 augmented the expression 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 subunit in response to TGF-beta 1. These findings, therefore, suggest that there is an inverse relationship between the malignancy and the expression mode of integrin subunits, especially alpha 2 subunit, in human salivary 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.