title: Heterogeneity for integrin expression and cytokine-mediated VLA modulation can influence the adhesion of human melanoma cells to extracellular matrix proteins.
abstract: Expression of alpha and beta 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-alpha I, VLA-alpha 2 and VLA-alpha 6 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-alpha 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-alpha subunits revealed that the presence on melanoma cells of VLA-alpha 2, VLA-alpha 5 and VLA-alpha 6 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-I beta, rTNF-alpha, rIFN-gamma or TGF-beta I 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-alpha-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.
authors.affiliation: Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Mortarini
authors.forename: A
authors.initials: A
authors.lastname: Anichini
authors.forename: G
authors.initials: G
authors.lastname: Parmiani
mesh_terms: D002448:Cell Adhesion; D003094:Collagen / Q000502:physiology*; D016207:Cytokines / Q000494:pharmacology*; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007797:Laminin / Q000502:physiology*; D008545:Melanoma / Q000737:chemistry / Q000473:pathology*; D009362:Neoplasm Metastasis; D009842:Oligopeptides / Q000502:physiology; D016029:Receptors, Very Late Antigen / Q000032:analysis / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D005353:Fibronectins; D007375:Interleukin-1; D007797:Laminin; D009842:Oligopeptides; D016029:Receptors, Very Late Antigen; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; C046617:arginyl-glycyl-aspartyl-serine