Cellular targets of exogenous tumour necrosis factor-alpha (TNF?) in human gliomas

Abstract

To identify the cellular targets of TNF alpha in human gliomas, a total of 30 surgical specimens (12 glioblastomas, 4 anaplastic astrocytomas, 3 astrocytomas, 7 brains adjacent to tumour (BAT), 4 histologically normal-appearing brains) were examined by in vitro binding technique using biotinylated TNF alpha. The TNF-binding sites (TNF-BS) were recognized in the tumour cells in 8 of the 12 glioblastomas, 3 of the 4 anaplastic astrocytomas and in all the 3 astrocytomas. The TNF-BS were also recognized in the vascular endothelial cells in all these cases. The presence of TNF-BS in blood vessels ranged from 7.7 to 74.4% of the background vessels. This wide range of variation in the presence of TNF-BS within the tumour cells and tumour blood vessels may be relevant to the variable response of individual tumours to TNF alpha therapy. Since the tissue of normal brain, which lacks TNF-BS, might hardly be affected by this cytokine, administration of TNF alpha may be considered as an adjuvant therapy in selected groups of patients.

Distribution of endogenous tumour necrosis factor alpha in gliomas.

“…'3 However, the tumour cells and endothelial cells in the t territory of tumour were shown to be the major targets of exogenous TNFa in human gliomas. 18 The present study demonstrated that cells containing TNFa protein were more abundant in malignant gliomas (AA, AOA, GB) than in benign ones (As, OA). Cells containing TNFa ells with protein have been detected in the brain tissues entre.…”

Emerging therapeutic targets for glioblastoma multiform

“…Since some gliomas regress in response to TNF-α, this cytokine has been considered as a candidate for adjunct treatment of these tumours. Cerebral intra-arterial TNF-α affects binding sites present only in tumour and not normal brain, enabling selective destruction of the tumour [18].…”