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This Article Full Text Full Text (PDF) All Versions of this Article: jcp.2005.031716v1 59/10/1052    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Abiatari, I Articles by Friess, H Search for Related Content PubMed PubMed Citation Articles by Abiatari, I Articles by Friess, H Pubmed/NCBI databases Medline Plus Health Information Pancreatic Cancer

Hsulf-1 regulates growth and invasion of pancreatic cancer cells

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

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