CNTF and its receptor subunits in human gliomas

Abstract

Ciliary neurotrophic factor (CNTF) promotes the survival of various neuronal cell populations. It is produced by astrocytes and influences the development and differentiation of glial cells. CNTF and related neuropoietic cytokines affect growth and differentiation of various neoplasms. Moreover, they induce the reactive transformation of astrocytes (gliosis) and influence growth and differentiation of neuroectodermal tumor cell lines in vitro. However, their role in gliomas is largely unknown. We studied the expression of CNTF and its receptor subunits in human astrocytomas and glioblastomas. In more than 95% of the tumors, CNTF transcripts were found by RNAase protection assay; in more than 80% of the cases, tumor cells were CNTF immunoreactive. CNTF receptor alpha (CNTFR alpha), the specific component of the tripartite CNTF receptor system, was detectable by Northern blot analysis in 80% of the cases. In situ hybridization revealed CNTFR alpha mRNA in the cytoplasm of neoplastic cells. Transcripts of the remaining two components of the CNTF receptor system, gp130 and LIFR beta, were found by Northern blotting in 83% and 70% of the tumors, respectively. Simultaneous expression of CNTF and all its receptor components was detected in approximately half of the tumors. These results indicate that CNTF and its receptor components are expressed by human glioma cells. The simultaneous expression of ligands and receptor subunits suggests that CNTF might act on human glioma cells via an auto- or paracrine mechanism.