Differences of reactivity to interferon gamma in HeLa and CaSki cells: a combined immunocytochemical and flow-cytometric study.

We characterized the changes induced by treatment for 48 h with 100 U/ ml interferon gamma (IFN-gamma) on HeLa and CaSki cells, derived from human uterine carcinomas and containing human papillomavirus (HPV) type 16 and HPV type 18 respectively, by studying cell growth, cell morphology, the cell cycle and expression of epidermal growth factor (EGF) receptor, filaggrin-profilaggrin and MHC class II antigen, HLA-DR. The response of the two cell lines to IFN gamma differed in some cases. In both cell lines, the cells remained viable; cell growth was similarly inhibited as shown by cell counts. Signs of morphological changes were essentially observed in HeLa cells. The cell cycle phases, analyzed by flow cytometry were more disturbed in CaSki than in HeLa cells; the proportion of CaSki cells in S phase increased and those in G2 + M decreased. Expression of EGF receptors related to proliferation increased only in CaSki cells while expression of filaggrin-profilaggrin, a marker of differentiation, and HLA-DR, a marker of epithelial cell immune response, was enhanced in both cell lines. The presence of filaggrin-profilaggrin being unexpected in these cells, the specificity of the reaction with the monoclonal antibody AKH1 was confirmed by immunoblotting. In conclusion, our results show that the two cell lines reacted differently to IFN gamma although they are of similar origin and the different antigens studied may be useful to predict the progression of lesions infected with HPV towards malignancy or the reactivity to IFN gamma of such lesions. However, enhanced synthesis of EGF receptors is probably independent of the antiproliferative effect of IFN gamma but an increase in HLA-DR antigen expression by epithelial cells, which corresponds to an immune response favored by IFN gamma, could act synergistically with cell growth inhibition and differentiation to exclude tumoral and/or HPV-infected cells.