Inhibitory effect of the lectin wheat germ agglutinin (WGA) on the proliferation of AR42J cells.
The rat pancreatic acinar tumour cell line AR42J is a widely used model to study the secretion, proliferation and differentiation of cells under the influence of hormones. These so-called amphicrine cells synthesize and secrete digestive enzymes as well as neuroendocrine peptides. They possess both subtypes of the highly glycosylated cholecystokinin (CCK) receptor which are important for the regulation of secretion and for cell growth. AR42J cells extrude CCK and gastrin-like hormone peptides and have the ability of an autostimulation (autocrine loop). The lectins wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA-I) bind to the glycosylated sites of these CCK receptors with the effect inhibiting CCK binding and thus inhibiting the CCK-induced Ca2+ release and alpha-amylase secretion. The so-called trophic hormones CCK and gastrin stimulate the secretion and proliferation of AR42J cells within the autocrine loop via autostimulation of their CCK receptors. In preceding papers, we described the inhibitory effect of WGA on the binding of 125I-CCK-8s to the CCK-A and -B receptors and the subsequent enzyme secretion of AR42J cells. In the present work, we studied the influence of the lectins WGA, UEA-I and galectin-1, as well as of the lectin-like enzyme alpha-amylase, on the proliferation of AR42J cells and prevention of autostimulation. The proliferation inhibition of the growth fraction was measured by estimation of the S-phase fraction by DNA flow cytometry. Whereas WGA inhibited the growth fraction significantly, UEA-I, human galectin-1 and human alpha-amylase had no significant effect. In transmission electron microscopy, we observed the accumulation of typical zymogen granules under the effect of WGA and a better differentiation of cells.
Ebert
Constanze
C
Department of Pathology, Electron Microscopic Centre, Medical Faculty, University of Rostock, Strempelstr. 14, Post Box 10 08 88, D-18055 Rostock, Germany.
Nebe
Barbara
B
Walzel
Hermann
H
Weber
Heike
H
Jonas
Ludwig
L
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D037483:Galectin 1 / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D046529:Microscopy, Electron, Transmission; D010179:Pancreas / Q000473:pathology / Q000648:ultrastructure; D037121:Plant Lectins / Q000494:pharmacology; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000737:chemistry; D022142:Secretory Vesicles / Q000648:ultrastructure; D014909:Wheat Germ Agglutinins / Q000494:pharmacology; D000516:alpha-Amylases / Q000494:pharmacology
D037483:Galectin 1; D037121:Plant Lectins; D011949:Receptors, Cholecystokinin; C036850:Ulex europaeus lectins; D014909:Wheat Germ Agglutinins; D000516:alpha-Amylases