THE POTENTIAL ROLE OF BASIC FIBROBLAST, GROWTH-FACTOR IN THE TRANSFORMATION OF CULTURED PRIMARY HUMAN FETAL ASTROCYTES AND THE PROLIFERATION OF HUMAN GLIOMA (U-87) CELLS

BASIC FIBROBLAST GROWTH factor (bFGF) is a potent stimulator of angiog enesis, proliferation, and invasion in human gliomas. To test the hypo thesis that bFGF is important in the development of the malignant phen otype of human gliomas, bFGF expression was prospectively modulated in primary human fetal astrocytes and in an established human glioma cel l line. Fetal astrocytes were transfected with a vector expressing bFG F modified by the addition of a secretory signal peptide sequence. Two of these bFGF astrocyte clones examined in vitro demonstrated anchora ge-independent growth, loss of contact inhibition, and decreased glial fibrillary acidic protein immunoreactivity, changes consistent with c ellular transformation. To analyze the inhibition of bFGF expression, phosphore-thioated bFGF antisense oligodeoxynucleotides were added to cultures of the U-87 human glioma cell line. The U-87 cell proliferati on was inhibited to 70.6 +/- 0.4% of control at 10 mu Lmol/L and to 53 .2 +/- 5.6% of control at 20 mu mol/L (P < 0.05). Both the 7.0- and 4. 0-kilobase bFGF messenger ribonucleic acid transcripts were reduced af ter exposure to the antisense oligodeoxynucleotide, and cell-associate d bFGF protein was reduced by 44%. The sense oligodeoxynucleotide, a n egative control, failed to inhibit U-87 proliferation. These data supp ort the concept that bFGF expression could be a key event in glial tum origenesis that may be necessary for the sustained growth of human gli omas.