Expression of α and β subunits of VLA and VNR integrins was analyzed by cytofluorimetric analysis on 6 different human primary and metastatic melanoma cell cultures. Marked inter-tumor heterogeneity was observed, and expression of VLA-α1, VLA-α2 and VLA-α6 was lower on primary melanomas than on metastatic lesions. The function of VLA products on melanoma cells was assessed by adhesion assays to extracellular matrix (ECM) proteins using a panel of melanoma clones previously characterized for the presence and heterogeneity of expression of the distinct VLA-α subunits. These experiments indicated that intra-tumor heterogeneity in the integrin profile can influence the interaction of neoplastic cells with ECM proteins. Inhibition of adhesion with antibodies to VLA-α subunits revealed that the presence on melanoma cells of VLA-α2, VLA-α5 and VLA-α6 is relevant for the adhesion to type-IV collagen, fibronectin and laminin respectively. Culture of tumor cells in the presence of cytokines such as rIL-1β, rTNF-α, rIFN-γ or TGF-β1 could induce up- or down-modulation in the level of expression of multiple VLA integrins. Cytokine-mediated antigenic shifts in the VLA profile of melanoma cells were detected by cytofluorimetric analysis as early as 24 hr after cytokine exposure. The cytokine-dependent change in the matrix receptor profile of melanoma cells also affected the adhesion to ECM proteins as revealed by the enhanced adhesion of rTNF-α-treated cells to fibronectin. These data indicate that constitutive heterogeneity in the integrin profile or cytokine-mediated shifts in VLA expression can affect the ability of human melanoma cells to interact with different ECM components.
|Number of pages||9|
|Journal||International Journal of Cancer|
|Publication status||Published - 1991|
ASJC Scopus subject areas
- Cancer Research