Insulin and insulin-like growth factors (IGF-1 and -2 or somatomedins) are anabolic effectors in many tissues and cultured cells including astrocytes and neurons. Receptors for insulin and IGFs are found throughout the human brain. Receptors for several growth factors are increased in tumor vs. normal tissue and this discrepancy may have therapeutic value in targeting toxic agents to tumor cells. To evaluate the potential role of IGFs in human CNS tumors, we examined the level of insulin and IGF receptors in tumors (astrocytomas and glioblastomas) and in normal brain. Although all surgical specimens contain receptors for all three growth factors, the highest values were observed with IGF-1 binding to glioma specimens. The IGF-1 receptor in tumor is the same size (118 kDa alpha-subunit) as the receptor. In normal brain, confirming the neural origin of the tumor cells expressing the IGF-1 receptor. Cultured cells derived from glioma specimens also express IGF-1 receptors, and many of these lines demonstrate a functional receptor as indicated by stimulation of DNA synthesis and receptor autophosphorylation in response to IGF-1. This demonstration of functional IGF-1 receptors in glioma cells suggests a role for this receptor in the regulation of glioma cell growth. In addition, high levels of high affinity IGF binding proteins (IGF BP) are produced by glioma cells. Certain characteristics of this IGF BP suggest it may be distinct from previously described IGF BPs, and thus may have a function specific for glioma cells.
