TY - JOUR
T1 - Interleukin-2 induces cell cycle perturbations leading to cell growth inhibition and death in malignant mesothelioma cells in vitro
AU - Porta, Camillo
AU - Danova, Marco
AU - Orengo, Anna Maria
AU - Ferrini, Silvano
AU - Moroni, Mauro
AU - Gaggero, Alessia
AU - Libener, Roberta
AU - Betta, Pier Giorgio
AU - Ferrari, Silvia
AU - Procopio, Antonio
AU - Strizzi, Luigi
AU - Mutti, Luciano
PY - 2000/9/12
Y1 - 2000/9/12
N2 - Previous report indicated that Interleukin-2 (IL-2) is able to inhibit the growth of IL-2-receptor-positive cancer cell lines without any involvement of the immune system, through IL-2-induced alterations of the cell cycle kinetics. In this study we provide evidence that IL-2 exerts anti-proliferative effect on three human malignant mesothelioma (MMe) cells in vitro, while no effects were observed on normal human mesothelial cell (HMC) primary cultures. The growth inhibitory effect of IL-2 on neoplastic cells appeared to depend on the baseline proliferative status of these cells. Indeed, in highly proliferating MMe cells, we observed a reduction of malignant cells in the S-phase of the cell cycle, with an accumulation in G0/G1, followed by apotosis for longer incubations or exposure to higher doses. On the contrary, in MMe cells proliferating at lower rate, IL-2 induces only a late cytotoxic effect, leading to apoptosis, without significantly affecting the cell cycle. IL-2Rβ mRNA was detectable by RT-PCR in all MMe cells, IL-2Rα mRNA in one only out the three assayed and IL-2Rγ mRNA in none. In addition, mRNA specific for the IL-2Rβ-associated Jak-1 tyrosine kinase was expressed in all MMe cell lines, further suggesting that IL-2Rβ may play a role in the observed effects. Very low, albeit detectable, levels of IL-2Rβ chain appeared to be expressed at the cell surface of MMe cells by indirect immunofluorescence and FACS analyses. Finally, Ca++ fluxes were rapidly induced when MMe cells were exposed to exogenous IL-2. (C) 2000 Wiley-Liss Inc.
AB - Previous report indicated that Interleukin-2 (IL-2) is able to inhibit the growth of IL-2-receptor-positive cancer cell lines without any involvement of the immune system, through IL-2-induced alterations of the cell cycle kinetics. In this study we provide evidence that IL-2 exerts anti-proliferative effect on three human malignant mesothelioma (MMe) cells in vitro, while no effects were observed on normal human mesothelial cell (HMC) primary cultures. The growth inhibitory effect of IL-2 on neoplastic cells appeared to depend on the baseline proliferative status of these cells. Indeed, in highly proliferating MMe cells, we observed a reduction of malignant cells in the S-phase of the cell cycle, with an accumulation in G0/G1, followed by apotosis for longer incubations or exposure to higher doses. On the contrary, in MMe cells proliferating at lower rate, IL-2 induces only a late cytotoxic effect, leading to apoptosis, without significantly affecting the cell cycle. IL-2Rβ mRNA was detectable by RT-PCR in all MMe cells, IL-2Rα mRNA in one only out the three assayed and IL-2Rγ mRNA in none. In addition, mRNA specific for the IL-2Rβ-associated Jak-1 tyrosine kinase was expressed in all MMe cell lines, further suggesting that IL-2Rβ may play a role in the observed effects. Very low, albeit detectable, levels of IL-2Rβ chain appeared to be expressed at the cell surface of MMe cells by indirect immunofluorescence and FACS analyses. Finally, Ca++ fluxes were rapidly induced when MMe cells were exposed to exogenous IL-2. (C) 2000 Wiley-Liss Inc.
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U2 - 10.1002/1097-4652(200010)185:1<126::AID-JCP12>3.0.CO;2-2
DO - 10.1002/1097-4652(200010)185:1<126::AID-JCP12>3.0.CO;2-2
M3 - Article
C2 - 10942526
AN - SCOPUS:0033846746
VL - 185
SP - 126
EP - 134
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
IS - 1
ER -