caa a22 4500 469074299 CHVBK 20180323132931.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF01741796 doi (NATIONALLICENCE)springer-10.1007/BF01741796 Phorbol 12-myristate 13-acetate induces resistance of human melanoma cells to natural-killer-and lymphokine-activated-killer-mediated cytotoxicity [Elektronische Daten] [Pierpaolo Correale, Antonio Procopio, Luigi Celio, Michele Caraglia, Geppino Genua, Vincenzo Coppola, Stefano Pepe, Nicola Normanno, Immacolata Vecchio, Giovannella Palmieri, Stefania Montagnani, Pierosandro Tagliaferri, Angelo Bianco] Summary: Human melanoma cells are sensitive to the lytic activity of natural killer (NK) and lymphokine-activated killer (LAK) cells in vitro. The events resulting in tumour cell killing by lymphocytic effectors have not been completely clarified, and the same target cell determinants regulating responsiveness to immune cytolysis have not yet been identified. Indeed, changes in the differentiative status of leukemia cells as well as in the expression of major histocompatibility complex (MHC) antigens have been described to modulate sensitivity to cytotoxic effectors; moreover surface expression of adhesion factors or extracellular matrix proteins by the cancer cells can promote the activation of the cytolytic effectors and has been described to correlate with tumour cell sensitivity to cytolytic cells. We reasoned that treatment with differentiation inducers could modulate melanoma cell sensitivity to NK and LAK cells. The present study demonstrates that human melanoma GLL-19 cells, when treated with the phorbol diester phorbol 12-myristate 13-acetate (PMA) in vitro, undergo growth inhibition and neuron-like differentiation. Moreover PMA treatment induces an evident inhibition of GLL-19 cell sensitivity to NK- and LAK-mediated cytotoxicity. GLL-19 cells express constitutively MHC class I antigens. PMA treatment, however, does not modify the expression of MHC class I and class II DR antigens in human melanoma GLL-19 cells. We have finally evaluated the effects of PMA on the expression at the cell surface of adhesion factors such as ICAM-1, and extracellular matrix proteins such as collagen IV, laminin and fibronectin; we have also studied the expression of the integrin vitronectin receptor, a membrane receptor for adhesive proteins. While adhesion factors and extracellular matrix proteins appear to play an important role in the interaction between immune effector and tumour target, it can be supposed that the modulation of such membrane-associated proteins or glycoproteins induces NK and LAK resistance in cancer cells. We indeed found that PMA treatment induced in GLL-19 a marked reduction of membrane expression of collagen IV and ICAM-1; moreover PMA reduced the cell membrane expression of the integrin vitronectin receptor. On the other hand, membrane expression of fibronectin and laminin was not affected by PMA. These data indicate that the acquisition of a NK- and LAK-resistant phenotype by GLL-19 cells occurs together with cell differentiation, down-regulation of membrane expression of collagen IV, ICAM-1 and vitronectin receptor, but in the absence of changes in MHC antigens. Springer-Verlag, 1992 Phorbol ester nationallicence LAK cells nationallicence Tumour cells nationallicence Cytotoxicity nationallicence Correale Pierpaolo Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut Procopio Antonio Dipartimento di Medicina Sperimentale, Universita' dell' Aquila, L'Aquila, Italy aut Celio Luigi Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut Caraglia Michele Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut Genua Geppino Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut Coppola Vincenzo Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut Pepe Stefano Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut Normanno Nicola Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut Vecchio Immacolata Dipartimento di Medicina Sperimentale, Universita' dell' Aquila, L'Aquila, Italy aut Palmieri Giovannella Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut Montagnani Stefania Istituto di Anatomia, II Facolta' di Medicina, Universita' Federico II di Napoli, Napoli, Italy aut Tagliaferri Pierosandro Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut Bianco Angelo Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut Cancer Immunology, Immunotherapy Springer-Verlag 34/4(1992-07-01), 272-278 0340-7004 34:4<272 1992 34 262 https://doi.org/10.1007/BF01741796 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01741796 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Correale Pierpaolo Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut NATIONALLICENCE 700 1- Procopio Antonio Dipartimento di Medicina Sperimentale, Universita' dell' Aquila, L'Aquila, Italy aut NATIONALLICENCE 700 1- Celio Luigi Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut NATIONALLICENCE 700 1- Caraglia Michele Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut NATIONALLICENCE 700 1- Genua Geppino Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut NATIONALLICENCE 700 1- Coppola Vincenzo Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut NATIONALLICENCE 700 1- Pepe Stefano Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut NATIONALLICENCE 700 1- Normanno Nicola Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut NATIONALLICENCE 700 1- Vecchio Immacolata Dipartimento di Medicina Sperimentale, Universita' dell' Aquila, L'Aquila, Italy aut NATIONALLICENCE 700 1- Palmieri Giovannella Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut NATIONALLICENCE 700 1- Montagnani Stefania Istituto di Anatomia, II Facolta' di Medicina, Universita' Federico II di Napoli, Napoli, Italy aut NATIONALLICENCE 700 1- Tagliaferri Pierosandro Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut NATIONALLICENCE 700 1- Bianco Angelo Cattedra di Oncologia Medica, II Facolta' di Medicina, Universita' degli Studi di Napoli, Via S. Pansini 5, 80 131, Naples, Italy aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 34/4(1992-07-01), 272-278 0340-7004 34:4<272 1992 34 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer