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Hsulf-1 regulates growth and invasion of pancreatic cancer cells.

Abiatari, Ivane and Kleeff, J and Li, J and Felix, K and Büchler, M W and Friess, H (2006) Hsulf-1 regulates growth and invasion of pancreatic cancer cells. Journal of clinical pathology, 59 (10). pp. 1052-8. ISSN 0021-9746

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Abstract

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.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Depositing User: Dr Ivane Abiatari
Date Deposited: 30 Apr 2015 05:28
Last Modified: 30 Apr 2015 05:28
URI: http://eprints.iliauni.edu.ge/id/eprint/2210

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