[Growth control of a human glioma cell line by multiple autocrine loop blockade]

Autocrine growth due to dysregulation of growth factor production may have a role in the development of neoplasia. We demonstrated that U251MG, a well characterized human malignant glioma cell line, had high affinity receptors for epidermal growth factor (EGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) by enzyme-linked immunosorbent assay. We assessed the inhibitory effect of anti-EGF receptor (EGFR), anti-FGF, and anti-PDGF monoclonal antibodies (MoAbs) on the growth of U251MG cells using the MTT assay and 3H thymidine uptake. At 50 micrograms/ml, the EGFR, FGF, and PDGF MoAbs significantly decreased cell numbers by 31.0%, 31.2%, and 31.0%, respectively, when compared to control cultures in the MTT assay. At the same concentration, the EGFR, FGF, and PDGF MoAbs reduced 3H thymidine uptake by 45.2%, 41.1%, and 40.0%, respectively, when compared to control cultures. At 50 micrograms/ml, a combination of the 3 MoAbs (16.6 micrograms/ml each) caused a 13.7% greater decrease in cell numbers in the MTT assay and an 11.9% greater decrease of 3H thymidine uptake. These findings suggest that the antigrowth factor MoAbs interrupted the autocrine loop at the growth factor receptor level. In conclusion, the demonstration that MoAbs directed against EGFR, FGF, and PDGF inhibit the growth of malignant glioma cells in vitro raises the possibility that these antibodies could be used clinically to treat malignant glioma either alone or conjugated to other agents.