Abstract
Glioblastoma multiforme (GBM) is the most malignant form of central nervous system tumor. Growth factors that are included as a supplement in a conditioned media is essential for culturing GBM cells. We discovered a subset of patient-derived cells that exhibit high cellular proliferation in the absence of supplemental growth factors. In order to identify autocrine growth factors that govern tumor cell growth, we utilized proteomics analysis from the growth-factor free conditioned media from two GBM cells and identified Midkine (MDK) as one of the prominent cytokines during GBM proliferation. Midkine is a major secretome in excess of 300 proteins. We inhibited tumor cells using recombinant lentiviral vector of MDK or neutralizing antibody. After MDK expression level was suppressed in vitro, cell cycle and cell proliferation rate were significantly down-regulated as well. Furthermore, pathway analysis has revealed specific pathways that are associated with reactive oxygen species stress were up-regulated.
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