Abstract
Neuron specific enolase (NSE) is widely used as a neuro-endocrine marker. However the presence of NSE in many non-neuroendocrine tissues has raised questions on the specificity of NSE. We have investigated NSE immunoreactivity (NSA-ag), gamma-enolase activity and total enolase activity in small cell lung cancer (SCLC) cell lines. During well-controlled exponential growth comparison of NSE-ag content and gamma-enolase activity with the doubling-time (Td) and NSE-ag content with gamma-enolase and total enolase activity led to a clear distinction of two types of cell line: variant cell lines plus part of the classic cell lines (type I) and the remaining classic cell lines (type II). The distinction was based upon both an abrupt 6-fold increase of gamma-enolase activity and an 18-fold increase of NSE-ag, which for the larger part was enzymatically inactive. Within each group the increase of NSE-ag content was significantly correlated with the increase of gamma-enolase activity and both NSE-ag content and gamma-enolase activity increased linearly with Td. It is concluded that gamma-enolase seems to be associated with the regulation of growth rate and that a compound with the gamma-enolase antigen but without enzyme activity can distinguish two different classes of SCLC cell lines. Furthermore the demonstration that NSE-ag can represent the active enzyme as well as an enzymatically inactive compound may explain why a controversy about neuron- or non-specificity of NSE exists.
Highlights
We have investigated the relationship between Neuron specific enolase (NSE)
ENZYMATICALLY INACTIVE NSE IN small cell lung cancer (SCLC)-CELL LINES 1067 showed only immunoreactivity migrating on gel as Wenolase
It has been shown to be a clinically reliable tool to monitor the course of the disease (Cooper et doubling-time of NSE at relapse was highly significantly correlated with survival from time of relapse (Splinter et al, 1987b) and pretreatment-values were shown to have prognostic value by some (J0rgenson et al, 1988), but not by others (Van der Gaast et al, 1991)
Summary
The SCLC-cell lines were generously provided by the Dept. of Clinical Immunology, University of Groningen, The Netherlands. The mean ALAAD-activity of only the classic cell lines in both groups was similar (0.805 ± 0.574 and 0.818 ± 0.606 mU 10-6 cells, P = 0.9) and the mean enolase-activity of the left and the right group was 0.856 ± 0.213 and 0.624 ± 0.117 U mg-' protein respectively (P = 0.02). The mean ratio for type I cell lines was 635 ± 144 ng U ' and for the right group 2994 ± 350 ng U-' (P
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