PRODUCTS OF CELLS FROM GLIOMAS .9. EVIDENCE THAT 2 FUNDAMENTALLY DIFFERENT MECHANISMS CHANGE EXTRACELLULAR-MATRIX EXPRESSION BY GLIOMAS

Four human astrocytic gliomas of high grade of malignancy were each ev aluated in tissue and in vitro for percentages of cells expressing gli al fibrillary acidic protein (GFAP), collagen type IV, laminin and fib ronectin assessed by immunofluorescence with counterstaining of nuclea r DNA. Percentages of cells with reticulin and cells binding fluoresce in-labeled Ulex europaeus agglutinin were also assessed. In tissue, ea ch extracellular matrix (ECM) component was associated with cells in t he walls of abnormal proliferations of glioma vessels, and all four tu mors had the same staining pattern. Two strikingly different patterns of conversion of gene product expression emerged during in vitro culti vation. (1). In the most common pattern, percentages of all six marker s consistently shifted toward the exact phenotype of mesenchymal cells in abnormal vascular proliferations: increased reticulin, collagen ty pe IV,laminin and fibronectin; markedly decreased glial marker GFAP an d absent endothelial marker Ulex europaeus agglutinin. The simplest ex planation of this constellation of changes coordinated toward expressi on of vascular ECM markers is that primary glioma cell cultures are ov ergrown by mesenchymal cells from the abnormal vascular proliferations of the original glioma. These cell cultures were tested for in situ h ybridization (ISH) signals of chromosomes 7 and 10. Cells from one gli oma had diploid signals. Cells from the other glioma had aneuploid sig nals indicating they were neoplastic; however, their signals reflected different numerical chromosomal aberrations than those common to neop lastic glia. (2). The second pattern was different. Cells with ISH chr omosomal signals of neoplastic glia retained GFAP, and gained collagen type IV. Their laminin and fibronectin diminished, but persisted amon g a lower percentage of cells. Cloning and double immunofluorescence c onfirmed the presence of individual cells with glial and mesenchymal m arkers. A cell expressing GFAP in addition to either fibronectin, reti culin or collagen type IV is not a known constituent of glioblastoma t issue. This provides evidence of a second mechanism of conversion of g ene expression in gliomas.