Role of CD109 in glioma invasion
Pauliina Filppu, M.Sc. (1), Piia-Riitta Karhemo, Ph.D. (2), Maija Hyvönen, M.Sc. (1), Harri Sihto, Ph.D. (1), Heikki Joensuu, M.D., Ph.D. (1,3) Kaisa Lehti, Ph.D., (2) and Pirjo Laakkonen Ph.D., (1). 1. Research Programs Unit, Translational Cancer Biology, University of Helsinki, Finland. 2. Research Programs Unit, Genome-Scale Biology, University of Helsinki, Finland. 3. Helsinki University Central Hospital, Helsinki, Finland.
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. Due to its highly invasive nature, GBM is associated with high morbidity and mortality with median survival of only 12 months. CD109 is a GPI-anchored cell surface glycoprotein expressed by normal endothelial cells, platelets, activated T-cells as well as by some cancer cells, but its physiological function remains unknown. Our research group has recently identified CD109 as a novel metastasis-associated protein in metastatic melanoma and invasive breast carcinoma cells by comparative proteomics (Karhemo et al., 2012). The aim of this study is to understand the role of CD109 in glioma invasion and to study the relationship between CD109 and glioma stem cells.
Oncomine analysis revealed significantly higher CD109 mRNA expression in glioblastomas compared to the normal human brain. Based on our tumor microarray analysis, CD109 is expressed in gliomas in a grade-dependent manner. 90% of GBMs expressed CD109 while 80% of grade III and only 50% of grade II tumors were positive. Knockdown of CD109 decreased the expression of glioma stem cell markers and the ability to form colonies from single cells indicating association of CD109 with stemness. We have also observed that expression of CD109 affects glioma invasion in vitro. Knockdown of CD109 switched the invasion pattern from collective to single cell motility. Our studies will concentrate to reveal the molecular pathways and mechanisms involved in CD109 mediated glioma cell stemness and invasion.
Taken together, this study is expected to provide novel information on CD109 and on the poorly understood mechanisms underlying glioma invasion that will facilitate the development of novel therapeutic strategies for this deadly disease.Format: Poster