Molecular variants of epidermal growth factor in malignant astrocytoma

The present study has measured EGF levels in primary brain tumor tissues. EGF levels were measured by specific radioimmunoassay (RIA) and further analyzed by reversed-phase high performance liquid chromatography (RP-HPLC) followed by RIA and radioreceptor binding. The levels of EGF-like immunoreactivity (EGF-LI) in astrocytoma-IV tumors were fourfold greater than those in normal brain tissues. In astrocytoma-II and astrocytoma-III tumors, however, levels of EGF-LI were not different from those in normal brain. HPLC analysis of extracts from normal brain tissue and astrocytoma-II showed one peak of EGF-LI that coeluted with standard human EGF (retention time 22 min). Interestingly, EGF-LI in extracts of astrocytoma-IV tumors eluted in two distinct peaks with retention times of 24 and 26 min (Astro-A and Astro-B, respectively). Materials in both Astro-A and Astro-B peaks reduced the specific binding of [¹²⁵I]hEGF to EGF receptors in human placental membranes. These studies demonstrate elevated levels of EGF-LI in malignant astrocytoma, but not in benign tumors. Furthermore, two different EGF-like molecules that are different from native EGF are present in malignant astrocytoma.