Gangliocytes in neuroblastic tumors express alarin, a novel peptide derived by differential splicing of the galanin-like peptide gene.
In neuroblastic tumors a relationship of differentiation of the tumor to galanin receptor expression and antiproliferative and apoptotic effects upon activation of galanin receptors in neuroblastoma cells was reported. To elucidate the expression of other components of the galanin peptide family in neuroblastic tumors, RT-PCR analysis of a variety of human neuroblastic tumor tissues was performed. Ganglioneuroma tissues revealed the presence of a splice variant of the galanin-like peptide (GALP) mRNA, which results in exclusion of exon 3 and a frame shift after the signal peptide sequence of GALP. This generates a peptide of 25 amino acids, which we have termed alarin because of the N-terminal alanine and the C-terminal serine. The novel neuropeptide alarin does not reveal significant homology to other peptides. Immunohistochemistry with antibodies directed against synthetic alarin peptide detected specific cytoplasmic granular staining in ganglia of human ganglioneuroma and ganglioneuroblastoma, as well as differentiated tumor cells of neuroblastoma tissues. Undifferentiated neuroblasts of these tumor tissues did not show alarin-like immunoreactivity and alarin-specific mRNA. Our findings indicate that alarin expression is a feature of ganglionic differentiation in neuroblastic tumor tissues.
Santic
Radmila
R
Department of Pediatrics, Paracelsus Private Medical University Salzburg, A-5020 Salzburg, Austria.
Fenninger
Katrin
K
Graf
Kerstin
K
Schneider
Rainer
R
Hauser-Kronberger
Cornelia
C
Schilling
Freimut H
FH
Kogner
Per
P
Ratschek
Manfred
M
Jones
Neil
N
Sperl
Wolfgang
W
Kofler
Barbara
B
D000595:Amino Acid Sequence; D002675:Child, Preschool; D005260:Female; D019004:Galanin / Q000378:metabolism; D044089:Galanin-Like Peptide / Q000235:genetics / Q000378:metabolism*; D018305:Ganglioneuroblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D012326:RNA Splicing; D044088:Receptors, Galanin / Q000378:metabolism
D044089:Galanin-Like Peptide; D044088:Receptors, Galanin; D019004:Galanin