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


CONCLUSIONS
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.
Schrader
Jörg
J
Department of Neurology, University of Marburg, Marburg, Germany. jschrade@uke.uni-hamburg.de
Deuster
Oliver
O
Rinn
Birgit
B
Schulz
Martina
M
Kautz
Andreas
A
Dodel
Richard
R
Meyer
Bernhard
B
Al-Abed
Yousef
Y
Balakrishnan
Karthikeyan
K
Reese
Jens P
JP
Bacher
Michael
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003260:Contact Inhibition / Q000187:drug effects / Q000235:genetics*; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D018390:Gene Targeting; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection
D000970:Antineoplastic Agents; D008263:Macrophage Migration-Inhibitory Factors; D034741:RNA, Small Interfering; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human