Interleukin-2 induces cell cycle perturbations leading to cell growth inhibition and death in malignant mesothelioma cells in vitro

Camillo Porta, Marco Danova, Anna Maria Orengo, Silvano Ferrini, Mauro Moroni, Alessia Gaggero, Roberta Libener, Pier Giorgio Betta, Silvia Ferrari, Antonio Procopio, Luigi Strizzi, Luciano Mutti

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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.

Original languageEnglish
Pages (from-to)126-134
Number of pages9
JournalJournal of Cellular Physiology
Issue number1
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology


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