Conflicting evidences suggested that levels of HLA-A and -B antigens expressed on normal and neoplastic cells of given individuals are genetically predetermined, or, on the other hand, regulated by molecular mechanisms generating the down regulated expression of HLA-B antigens frequently observed on melanoma cells. In our study, we quantitated, both at the protein and mRNA level, the amounts of HLA-A and -B antigens constitutively expressed on 23 primary cultures of metastatic melanomas and on autologous peripheral blood mononuclear cells (PBMC). Flow cytometric analyses identified a significantly (p < 0.01) lower expression of HLA-B antigens on melanoma cell cultures but not on autologous PBMC. Consistently, lower amounts of HLA-B antigens mRNA were detected by RNase protection assay exclusively in neoplastic cells. This unbalanced expression of HLA-A and -B antigens was readily reverted by interferon (IFN)-<gamma> but not by the DNA hypomethylating agent 5-aza-2'-deoxycytidine in 4 melanoma cell cultures investigated. Significantly (p < 0.05) lower levels of HLA-B antigens were also detected on cells from solid malignancies of different histotypes but not on neoplastic cells from hemopoietic neoplasms; levels of HLA-B antigens were rapidly up-regulated by IFN-<gamma> exclusively on non-hemopoietic transformed cells. Together, these data strongly argue against a genetic predetermination of the amounts of HLA-A and -B antigens expressed on normal and neoplastic cells of distinct melanoma patients and suggest that constitutively low levels of HLA-B antigens are a specific feature of non-hemopoietic transformed cells that is controlled by common regulatory mechanism(s) and that is possibly shared by non-hemopoietic normal cells. (C) 2001 Wiley-Liss.
Gasparollo, A., Coral, S., Ciullo, M., Prisco, A., Cattarossi, I., Sigalotti, L., et al. (2001). Unbalanced expression of HLA-A and -B antigens: A specific feature of cutaneous melanoma and other non-hemopoietic malignancies reverted by IFN-gamma. INTERNATIONAL JOURNAL OF CANCER, 91(4), 500-507 [10.1002/1097-0215(200002)9999:9999<::AID-IJC1076>3.3.CO;2-9].
Unbalanced expression of HLA-A and -B antigens: A specific feature of cutaneous melanoma and other non-hemopoietic malignancies reverted by IFN-gamma
Maio M
2001-01-01
Abstract
Conflicting evidences suggested that levels of HLA-A and -B antigens expressed on normal and neoplastic cells of given individuals are genetically predetermined, or, on the other hand, regulated by molecular mechanisms generating the down regulated expression of HLA-B antigens frequently observed on melanoma cells. In our study, we quantitated, both at the protein and mRNA level, the amounts of HLA-A and -B antigens constitutively expressed on 23 primary cultures of metastatic melanomas and on autologous peripheral blood mononuclear cells (PBMC). Flow cytometric analyses identified a significantly (p < 0.01) lower expression of HLA-B antigens on melanoma cell cultures but not on autologous PBMC. Consistently, lower amounts of HLA-B antigens mRNA were detected by RNase protection assay exclusively in neoplastic cells. This unbalanced expression of HLA-A and -B antigens was readily reverted by interferon (IFN)-I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/1081426
Attenzione
Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo