Abnormal production of the TNF-homologue APRIL increases the proliferation of human malignant glioblastoma cell lines via a specific receptor

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Abstract
A proliferation-inducing ligand (APRIL) of the tumour necrosis factor (TNF) family is produced in small amounts in many tissues and more abundantly in tumours. APRIL has been reported to promote cell growth in vivo and in vitro. It was recently shown that the production of APRIL in some glioblastoma cell lines does not lead to an increase in cell growth. In this study, we investigated the production of APRIL and its ability to increase the proliferation of eight human glioblastoma cell lines. We found that APRIL was produced in the eight human glioblastoma cell lines tested but not in the normal embryonic astrocyte counterparts of glioblastomas. Flow cytometry demonstrated the presence of a specific APRIL-binding receptor on the cell surface in all the glioblastoma cell lines tested. This receptor was also present on normal embryonic and adult astrocytes and embryonic neural progenitor cells. Moreover, the addition of recombinant human APRIL resulted in an increase in proliferation rate of normal adult astrocytes and in four of eight cell lines tested. Addition of the soluble recombinant TNF-receptor-homologue B-cell maturation (BCMA) chimeric protein, which binds APRIL, confirmed the involvement of APRIL in the growth of malignant glioblastoma cell lines.