Effect of Interferon‐Gamma on the Expression of HLA‐DR by Human Melanoma Cells of Varying Metastatic Potential

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Abstract
Three human melanoma cell lines of varying invasive and metastatic potential were analyzed for their ability to express HLA‐DR antigens on the cell surface as well as transcriptionally at the mRNA level in the presence and absence of IFN‐γ treatment. Cells of low and intermediate metastatic and invasive potential showed a high percentage of HLA‐DR surface expression, both before (91.2‐99.9%) and after (97.8‐99.9%) IFN‐γ treatment, as quantitated by flow cytometry. In contrast, cells of high metastatic and invasive potential expressed barely detectable levels of HLA‐DR‐positive cells before IFN‐γ treatment (0.3‐0.6%) and displayed elevated levels following treatment (42.3‐89.4%(. Allowing the highly metastatic cells to recover for 7 or 14 days following IFN‐γ treatment resulted in barely detectable levels of HLA‐DR‐positive cells. Northern blot analyses of HLA‐DR transcription levels showed a strong expression in cells of low and intermediate metastatic and invasive potential. HLA‐DR mRNA levels were not detectable in control cells of high metastatic potential nor in those cells which had undergone 7‐ and 14‐day recovery periods following IFN‐γ treatment. There was, however, an induction of HLA‐DR expression in the cells that had been treated with IFN‐γ for 72 hr and allowed no recovery period. In addition, a punctate, receptor‐like pattern of immunofluorescence staining pattern for cell surface HLA‐DR was seen after a 72 hr IFN‐γ treatment in the highly metastatic cells. In contrast, cells of low and intermediate metastatic potential expressed a homogeneous ring‐like pattern of antigen expression.