Astroglial growth factors in normal human brain and brain tumors: comparison with embryonic brain

Aqueous extracts of 18-day embryonic chicken brains, 15-day embryonic and adult rat brains and human brain tumors, as well as control histologically-normal adult human brain taken from around brain tumors or around arteriovenous malformations each stimulated the growth of cultured chick astrocytes. Eight mitogenic fractions were separated reproducibly by Bio-Gel P-10 molecular seive chromatography. They had apparent molecular weights (M.W.) of 24, 17, 12, 9, 5, 2.8, 1.4 and 1.2 kD. The activity of each fraction was concentration dependent. The fractions did not appear to be artifactually derived by proteolysis from a larger mitogen since (i) protease inhibitors were added at the time of homogenization to prevent degradation, (ii) protease treatment did not produce large quantities of the lower molecular weight fractions, (iii) incubation of brain extracts for up to four hours at 30° C did not alter the activity of the various mitogenic fractions and (iv) addition of albumin to inhibit protease activity similarly did not change the profile of the factors. In contrast, treatment with protease reduced the activity of all the factors although those with M.W. of 5 and 1.2 kD were inactivated more slowly than the others. The various fractions were stable when rechromatographed. This suggested they were not chance aggregates derived artifactually during extraction but rather might have physiological and pathological roles. The activities of each mitogenic fraction were significantly higher in brain extracts from embryonic rats than in those from adult rats. In brain extracts of rat and chicken embryos the fractions of lower M.W. 5 kD to 1.2 kD were relatively abundent. In contrast in brain extracts from adult rats the predominant mitogenic fractions had apparent M.W. of 24,17 and 12 kD. In histologically normal adult human brain taken from around the tumors or around arteriovenous malformations the 5 kD fraction was present in small amounts and the fractions of lower molecular weight were present in very small amounts. In human glial brain tumors there was a preponderance of the 5 kD activity and more of the 2.8 and 1.4 kD activity fractions than in histologically normal adult human brain. But there was relatively less activity in the 24 and 17 kD fractions. The growth factor profile of human meningiomas was quite different from that of histologically normal human brain or human glial brain tumors. The fraction from meningiomas that was most mitogenic for astrocytes had a molecular weight of 12 kD. Although the higher molecular weight factors may represent already described growth factors derived from brain, the lower molecular weight factors have not been reported previously.