Human melanoma cells with high susceptibility to cell-mediated lysis can be identified on the basis of ICAM-1 phenotype, VLA profile and invasive ability.
Marked heterogeneity for susceptibility to lysis by autologous CTL clones and allogeneic IL-2-activated CD3- and CD3+ lymphocytes was found among 19 clones isolated from a human metastatic melanoma (Me665/2). A subset of 5 clones with the highest susceptibility to lysis had increased ICAM-1 antigen expression. Phenotype analysis for the presence of extracellular matrix receptors in the beta 1- and beta 3-integrin families revealed that the tumor clones with the highest susceptibility to lysis were also characterized by frequent expression or increased expression of multiple receptors in the beta 1 family including VLA-1, -2, -3, -4 and -6. The correlation between phenotypic markers and susceptibility to lysis, seen at the clonal level, was confirmed by selection experiments on the uncloned metastasis Me665/2. In fact, the neoplastic population surviving 3 cycles of immunoselection with IL-2-activated lymphocytes exhibited, in comparison to the unselected metastasis: (1) reduced susceptibility to lysis and (2) reduced expression of ICAM-1 and of VLA antigens. In contrast, enhanced susceptibility to lysis and up-regulation of ICAM-1, VLA-1 and VLA-3 antigens were observed on melanoma cells recovered after invading a reconstituted basement membrane. These data indicate that melanoma cells with enhanced susceptibility to cell-mediated lysis can be identified on the basis of phenotypic characteristics (ICAM-1 and VLA antigen profile) and functional features (invasive ability on reconstituted basement membranes).
Anichini
A
A
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Mortarini
R
R
Supino
R
R
Parmiani
G
G
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002470:Cell Survival; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000276:immunology; D010641:Phenotype; D016029:Receptors, Very Late Antigen / Q000032:analysis*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016023:Integrins; D007376:Interleukin-2; D016029:Receptors, Very Late Antigen; D018799:Intercellular Adhesion Molecule-1