Overexpression of midkine contributes to anti‐apoptotic effects in human meningiomas

Abstract

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.

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

“…MDK shows highly increased expression in a number of malignant tumors (Nakagawara et al, 1995;O'Brien et al, 1996;Mishima et al, 1997;Ye et al, 1999;Ikematsu et al, 2000;Jia et al, 2007;Maeda et al, 2007) and enhances tumor progression by promoting survival, growth, migration and angiogenic activity Takei et al, 2001;Kadomatsu and Muramatsu, 2004;Mirkin et al, 2005;Tong et al, 2007). In human brain tumors, especially MDK is overexpressed during tumor progression, and patients whose tumors express a higher level of MDK have a worse prognosis (Mishima et al, 1997).…”

Evaluation of midkine expression in dentigerous cysts, odontogenic keratocysts and different types of ameloblastoma

“…Increase and changes in Midkine expression were also reported in other diseases and cancers, namely esophageal squamous cancer (14,17,18,23), squamous cell carcinoma (24), and meningioma (25). This proves its role as a candidate gene in targeted therapy.…”

SP100 reduces malignancy of human glioma cells

“…The human glioblastoma cell lines were obtained from the DKFZ (Heidelberg, Germany; U118, U343, U373, A172, T98G) or were generated in our laboratory (A739, A776, A764, 7/06, 9/99, 19/07, 27/07, 43/07) by dissociation and cultivation in Dulbeccos's modified Eagle's medium (DMEM; Invitrogen, Karlsruhe, Germany) plus 10% fetal calf serum (FCS; Invitrogen) as previously described (19)(20)(21). Human meningioma cell lines (M15, M16, M17, M19, M22) were also generated in our laboratory and cultured in DMEM plus 20% FCS (22). The different cell lines were checked for purity by immunostaining with cell type-specific markers and for the absence of Mycoplasma contamination by staining with bisbenzimide as described (21,22).…”

“…Human meningioma cell lines (M15, M16, M17, M19, M22) were also generated in our laboratory and cultured in DMEM plus 20% FCS (22). The different cell lines were checked for purity by immunostaining with cell type-specific markers and for the absence of Mycoplasma contamination by staining with bisbenzimide as described (21,22). Stimulation experiments.…”