Secretion of alpha 2-macroglobulin, alpha 2-antiplasmin, and plasminogen activator inhibitor-1 by glioblastoma multiforme in primary organ culture.
Explants from a glioblastoma multiforme were maintained for 4 weeks in a three-dimensional Gelfoam matrix culture in order to study the synthesis of alpha 2-antiplasmin (alpha 2AP), alpha 2-macroglobulin (alpha 2M), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA). Since the organ culture system promotes cellular differentiation in gliomas with increasing time in vitro, secretion of the proteinase inhibitors and t-PA was examined at weekly intervals. Increased immunohistochemical staining for glial fibrillary acidic protein, a marker of astroglial differentiation, was observed in the explants with advancing time in culture. The proteinase inhibitors alpha 2AP and alpha 2M were secreted into the medium in all 4 weeks, while PAI-1 was detected at significant concentrations by an enzyme-linked immunosorbent assay (ELISA) in Weeks 3 and 4 only. The quantity of each inhibitor secreted into fresh medium during a 24-hour interval increased with the age of the tumor explants in the Gelfoam culture system. At no time was a sensitive ELISA able to detect t-PA in the culture medium. This study demonstrates that glioblastoma multiforme cells in primary organ culture can secrete three major fibrinolysis proteinase inhibitors. The appearance of PAI-1 only after extensive culturing of the explants suggests a possible correlation with neoplastic astroglial maturation.
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville.
M E
ME
Keohane
S W
SW
Hall
S R
SR
VandenBerg
S L
SL
Gonias
D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009924:Organ Culture Techniques; D015849:Plasminogen Inactivators / Q000032:analysis / Q000378:metabolism*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000032:analysis; D000979:alpha-2-Antiplasmin / Q000032:analysis / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000032:analysis / Q000378:metabolism*
D015849:Plasminogen Inactivators; D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; D010959:Tissue Plasminogen Activator