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The role of MDGI in gliomas

Maija Hyvönen 1, Pauliina Turunen 2, Pauliina Filppu 1, Kaisa Lehti 2 and Pirjo Laakkonen 1. 1) Research Programs Unit, Translational Cancer Biology, University of Helsinki, Finland. 2) Research Programs Unit, Genome-Scale Biology, University of Helsinki, Finland.

Despite of advances in cancer therapies, the prognosis of high-grade glioma patients is poor. Therefore, to develop new therapeutics, it is vital to clarify mechanisms driving the progression of these tumors. We have recently identified a homing peptide, which, after systemic delivery, specifically accumulates to malignant brain tumors and their vasculature. Mammary-derived growth inhibitor (MDGI) was identified as an interacting partner of the peptide. MDGI is a fatty acid binding protein, whose role in cancer is currently unclear.

MDGI´s expression was analyzed in human glioma cell lines using Western blot and it´s clinical relevance in glioblastoma and glioma patients was studied with immunohistochemistry. In addition, both overexpressing of MDGI (U87MG) and its silencing (BT12, BT13) in glioma cell lines were used in in vitro and ex vivo functional studies.

Abundant MDGI expression was detected in glioma neurospheres derived from all patients tested. In addition, 50% of the patient samples showed MDGI positive staining. Importantly, MDGI expression also significantly correlated with poorer overall 5-year survival of the glioma patients.

The invasion and colony formation of MDGI overexpressing cells were significantly enhanced. Importantly, even more striking changes were observed in the morphology of MDGI silenced cells, which failed to form multicellular spheroids (Figure 1). These cells were apoptotic and their proliferation, viability and colony formation were also significantly reduced.

Our results suggest MDGI to be a novel marker for gliomas and crucial for glioma cell survival and growth. Due to MDGI´s previously described functions in cell metabolism it is most likely important for glioma cell bioenergetics as well.

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