ORIGINAL ARTICLE

Hsulf-1 regulates growth and invasion of pancreatic cancer cells

I Abiatari, J Kleeff, J Li, K Felix, M W Büchler and H Friess

Department of General Surgery, University of Heidelberg, Heidelberg, Germany

Correspondence to:
Correspondence to:
J Kleeff
Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany;joerg_kleeff{at}med.uni-heidelberg.de

Background: Hsulf-1 is a newly identified enzyme with arylsulphatase activity that can regulate the sulphation state of cell-surface heparan sulphate proteoglycans (HSPGs). In vitro overexpression of this enzyme in pancreatic cancer cells decreases responsiveness to fibroblastic growth factor-2, as Hsulf-1 is up regulated in primary pancreatic adenocarcinoma.

Aim: To further analyse the functions of the Hsulf-1 enzyme in vitro and in vivo with respect to growth, invasion and tumorigenicity.

Methods and results: Transfection of Panc-1 pancreatic cancer cells with a full-length Hsulf-1 expression vector resulted in increased invasiveness and adhesiveness. An in vivo xenograft nude mouse tumour model showed a markedly reduced growth potential of Hsulf-1-expressing Panc-1 cells, which correlated with a considerably lower proliferation rate. Hsulf-1-positive nude mouse tumours showed better development of interstitial matrix structures, with increased blood vessel density in these tumours. In an orthotopic model, Hsulf-1-positive tumours exhibited enhanced local invasiveness. In human primary pancreatic cancers there was strong staining for sulphated HSPGs, which was markedly reduced in metastatic tissue samples.

Conclusion: Hsulf-1-mediated desulphation of HSPGs reduces the growth ability of Panc-1 pancreatic cancer cells, but increases the basal invasiveness of these cells, suggesting an important role of this enzyme in pancreatic cancer progression.

Abbreviations: DMEM, Dulbecco’s modified Eagle’s medium; HSPGs, heparan sulphate proteoglycans

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