Open Access Highly Accessed Research article

Restoration of contact inhibition in human glioblastoma cell lines after MIF knockdown

Jörg Schrader12, Oliver Deuster3, Birgit Rinn1, Martina Schulz2, Andreas Kautz3, Richard Dodel3, Bernhard Meyer4, Yousef Al-Abed5, Karthikeyan Balakrishnan3, Jens P Reese3 and Michael Bacher3*

Author Affiliations

1 Institute of Immunology, University of Marburg, Marburg, Germany

2 I. Medical Department, University Hospital Hamburg-Eppendorf, Hamburg, Germany

3 Department of Neurology, University of Marburg, Marburg, Germany

4 Department of Neurosurgery, Technical University Munich, Germany

5 Laboratory of Medicinal Chemistry, North Shore Long Island Jewish Research Institute, Manhasset, New York 11030, USA

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BMC Cancer 2009, 9:464  doi:10.1186/1471-2407-9-464

Published: 28 December 2009

Abstract

Background

Studies of the role of the cytokine macrophage-migration-inhibitory-factor (MIF) in malignant tumors have revealed its stimulating influence on cell-cycle progression, angiogenesis and anti-apoptosis.

Results

Here we show that in vitro targeting MIF in cultures of human malignant glioblastoma cells by either antisense plasmid introduction or anti-MIF antibody treatment reduced the growth rates of tumor cells. Of note is the marked decrease of proliferation under confluent and over-confluent conditions, implying a role of MIF in overcoming contact inhibition. Several proteins involved in contact inhibition including p27, p21, p53 and CEBPalpha are upregulated in the MIF antisense clones indicating a restoration of contact inhibition in the tumor cells. Correspondingly, we observed a marked increase in MIF mRNA and protein content under higher cell densities in LN18 cells. Furthermore, we showed the relevance of the enzymatic active site of MIF for the proliferation of glioblastoma cells by using the MIF-tautomerase inhibitor ISO-1.

Conclusion

Our study adds another puzzle stone to the role of MIF in tumor growth and progression by showing the importance of MIF for overcoming contact inhibition.