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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-07-0145v1 15/2/569    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Arvidsson, Y. Articles by Nilsson, O. Search for Related Content PubMed PubMed Citation Articles by Arvidsson, Y. Articles by Nilsson, O.

Y Arvidsson, Pathology, Lundberg Laboratory for Cancer Research, Göteborg, Sweden
E Andersson, Pathology, Lundberg Laboratory for Cancer research, Göteborg, Sweden
A Bergström, Pathology, Lundberg Laboratory for Cancer research, Göteborg, Sweden
M Andersson, Pathology, Lundberg Laboratory for Cancer research, Göteborg, Sweden
G Altiparmak, Pathology, Lundberg Laboratory for Cancer research, Göteborg, Sweden
A Illerskog, Pathology, Lundberg Laboratory for Cancer research, Göteborg, Sweden
H Ahlman, Pathology, Lundberg Laboratory for Cancer research, Göteborg, Sweden
D Lamazhapova, Biochemistry, University of cambridge, Cambridge, United Kingdom
O Nilsson, Pathology, Lundberg Laboratory for Cancer research, Göteborg, Sweden

Correspondence: Yvonne Arvidsson, Email: yvonne.arvidsson{at}gu.se

Abstract

We have examined the global gene expression profile of small intestinal carcinoids by microarray analysis. High expression of a number of genes was found including amyloid precursor like protein 1 (APLP1). Q-RTPCR and western blot analysis demonstrated higher expression of APLP1 in carcinoid metastases relative to primary tumours indicating a role of APLP1 in tumour dissemination. Tissue microarray analysis of a large number of gastroentero-pancreatic tumours demonstrated a high frequency of APLP1 expression and a low frequency of amyloid precursor protein 2 (APLP2) expression in NE tumours as compared to non-NE tumours at the same sites. Meta-analysis of gene expression data from a large number of tumours outside the gastrointestinal tract confirmed a correlation between APLP1 expression and NE phenotype where high expression of APLP1 was accompanied by downregulation of APLP2 in NE tumours. Cellular localization of APLP1, APLP2 and amyloid precursor protein (APP) in carcinoid cells (GOT1) by confocal microscopy demonstrated partial co-localization with synaptophysin. This suggests that the APP family of proteins is transported to the cell membrane by synaptic microvesicles and that they may influence tumour cell adhesion and invasiveness. We conclude that APLP1 is differentially upregulated in gastrointestinal NE tumours and that APLP1 may be important for the dissemination of small intestinal carcinoids. Identification of APLP1 in NE tumours offers a novel target for treatment and may also serve as a tumour-specific marker.