Overexpression of midkine contributes to anti-apoptotic effects in human meningiomas.
Meningiomas are the second most common intracranial tumours. Most meningiomas grow slowly; however, atypical and anaplastic meningiomas show an aggressive biological behaviour. Overexpression of growth factors is considered to be a cause of carcinogenesis. Midkine and pleiotrophin are heparin-binding growth factors that promote growth, survival, migration and differentiation of various target cells. Both molecules are highly expressed during human embryogenesis but are rarely seen in the adult. We show that in relation to normal dura and arachnoid tissues, midkine was overexpressed in meningiomas on the mRNA and protein level, whereas pleiotrophin was not. Thereby, not only the intact but also the truncated form of midkine could be observed. The expression of midkine receptors was variable in different samples. Midkine stimulation of cultured meningioma cells induced phosphorylation of Akt, whereas no increase in phosphorylation of p42/44 MAPK or p38 MAPK could be detected. Midkine did not influence the proliferation of meningioma cells in vitro, but it did protect meningioma cells from camptothecin-mediated apoptotic cell death through reduction in the amounts of active caspase-3. These findings provide evidence for the overexpression of midkine in meningiomas which contributes to protection from cell death in these second most common intracranial tumours.
Tong
Ying
Y
Department of Neurosurgery, University Medical Center Schleswig-Holstein, Kiel, Germany.
Mentlein
Rolf
R
Buhl
Ralf
R
Hugo
Heinz-Hermann
HH
Krause
Jörg
J
Mehdorn
H Maximilian
HM
Held-Feindt
Janka
J
D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002166:Camptothecin / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D000078792:Midkine; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D008562:Membrane Glycoproteins; D017978:Receptors, Growth Factor; C408049:midkine receptors; D000078792:Midkine; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases; D053148:Caspase 3; D002166:Camptothecin