Premium
Stimulation of thromboxane release from primary cell cultures derived from human astrocytic glioma biopsies
Author(s) -
Murphy Sean,
Welk Greg,
Thwin Soe Soe
Publication year - 1990
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.440030307
Subject(s) - biology , astrogliosis , astrocyte , endocrinology , thromboxane , medicine , stimulation , glial fibrillary acidic protein , immunology , central nervous system , platelet , immunohistochemistry
Stimulation of primary cultures of rat astrocytes with appropriate agents results in the mobilization of arachidonic acid from intracellular lipid pools and the synthesis of eicosanoids. Thromboxane A 2 is one of the major prostanoids released upon stimulation with calcium ionophore, phorbol esters, and ATP; but a number of other predicted effectors are inactive. In an attempt to understand the pathophysiological significance of eicosanoid release from astrocytes, primary cultures have been derived from human astrocytic glioma biopsies. The majority of cells in the cultures expressed glial fibrillary acidic protein (GFAP), frequently in conjunction with vimentin and fibronectin. Cell sorting revealed that a significant proportion of cells in the cultures from the high‐grade (malignant) tumors expressed epidermal growth factor receptor, indicative of neoplastic cells. Both effective and ineffective agents in rat cultures were tested for their ability to stimulate release of thromboxane from these gliomas, and also from cultures of medulloblastoma and ependymoma which contained significant numbers of GFAP‐positive cells. Only cells from the high‐grade tumors released thromboxane in response to the known effective stimuli. While the muscarinic agonist carbachol was ineffective, norepinephrine evoked thromboxane release from malignant astrocytomas. These data show that cells derived from malignant human gliomas retain the ability to release thromboxane upon stimulation and suggest that a transformation in receptor coupling might accompany neoplasia, such that the cells now respond to a previously ineffective agonist.