Document Detail


Interleukin-2 induces cell cycle perturbations leading to cell growth inhibition and death in malignant mesothelioma cells in vitro.
MedLine Citation:
PMID:  10942526     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-2Rbeta mRNA was detectable by RT-PCR in all MMe cells, IL-2Ralpha mRNA in one only out the three assayed and IL-2Rgamma mRNA in none. In addition, mRNA specific for the IL-2Rbeta-associated Jak-1 tyrosine kinase was expressed in all MMe cell lines, further suggesting that IL-2Rbeta may play a role in the observed effects. Very low, albeit detectable, levels of IL-2Rbeta 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.
Authors:
C Porta; M Danova; A M Orengo; S Ferrini; M Moroni; A Gaggero; R Libener; P G Betta; S Ferrari; A Procopio; L Strizzi; L Mutti
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  185     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-09-25     Completed Date:  2000-09-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  126-34     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Wiley-Liss, Inc.
Affiliation:
Laboratory of Cytometry and Cellular Therapies, A. Ferrata Institute of Internal Medicine and Medical Oncology, IRCCS San Matteo University Hospital, Pavia, Italy.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Cell Cycle / drug effects*
Cell Division / drug effects
Humans
Interleukin-2 / pharmacology*
Mesothelioma / pathology*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Interleukin-2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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