Expression of poly(ADP-ribose) polymerase and distribution of poly(ADP-ribosyl)ation in glioblastoma and in a glioma multicellular tumour spheroid model

Development of necrosis is a characteristic feature of glioblastoma but its pathogenesis remains poorly understood. The process of poly(ADP-ribosyl)at ion in response to DNA damage is mediated by poly(ADP-ribose) polymerase (P ARP) and results in NAD(+) depletion. The consequent ATP and energy depleti on may result in cell necrosis. Therefore PARP activation is a potential ca ndidate for a regulatory role in the pathogenesis of necrosis in glioblasto ma. This study investigated whether there might be a relationship between b oth PARP expression and poly(ADP-ribosyl)ation, and necrosis in glioblastom a. The pattern of expression of PARP and of poly(ADP-ribose) groups in an a rchival series of glioblastoma was examined using immunohistochemistry. The se parameters were also studied in multicellular tumour spheroids, derived from human glioma cell lines in which central necrosis develops with increa sing spheroid diameter. Poly(ADP-ribose) groups were expressed in peri-necr otic tumour cells in glioblastoma. In the spheroid model poly(ADP-ribosyl)a tion was seen centrally in pre-necrotic and necrotic cells with increasing spheroid diameter. PARP was widely expressed in viable tumour cells in the glioblastoma sections. In the spheroids, PARP expression, which was initial ly diffuse, became confined to the outer proliferative zone with increasing diameter. The pattern of expression of poly(ADP-ribose) groups in the sphe roids and in glioblastoma raises the possibility that poly(ADP-ribosyl)atio n may play a role in the development of necrosis in glioma. The high basal PARP expression in both glioblastoma and the spheroids suggests that this e nzyme may have additional roles in glioma cell biology.