ATPS-40FUNCTIONAL ROLES OF CD166/ALCAM IN GLIOBLASTOMA

Abstract

Prognosis of glioblastoma multiforme (GBM) patients still remains poor. To improve its prognosis, it is important to identify new therapeutic targets. CD166/ALCAM is a member of the immunoglobulin superfamily and is widely expressed in various tissues such as neurons, fibroblasts, endothelial cells. Furthermore it is also reported to be a colon cancer stem cell marker as well as mesenchymal stem cell marker. CD166/ALCAM is also expressed on endothelial cells and is involved in angiogenesis. In this study, we aim to analyze the functional roles of CD166/ALCAM in glioblastoma. Transfection of CD166/ALCAM siRNA to U87MG and U251 cells significantly increased cell invasion in matrigel invasion assay without affecting cell proliferation. Transfection of ALCAM shRNA to U87MG glioblastoma cells significantly increased the tumor vessel area of U87MG xenograft in immune-deficient mice. Furthermore, over-expression of soluble isoform of CD166/ALCAM in U87MG GBM cells promoted tumor progression in intracranial transplant to immune-deficient mice. We also found that CD166/ALCAM was highly expressed on the CD133+ glioblastoma stem cell populations. In the CD133+ glioblastoma cell population, CD166/ALCAM positive cells were highly enriched with tumor-sphere-initiating cells in vitro. In summary, CD166/ALCAM is involved in glioblastoma invasion, angiogenesis, and tumor progression in glioblastoma. In addition CD166/ALCAM can be a candidate for glioblastoma progenitor markers. All these findings suggest that CD166/ALCAM is a potent therapeutic target against glioblastoma.