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


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


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.


CONCLUSIONS
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.
Abiatari
I
I
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Kleeff
J
J
Li
J
J
Felix
K
K
Büchler
M W
MW
Friess
H
H
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000328:Adult; D000368:Aged; D000818:Animals; D002448:Cell Adhesion; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D015238:Sulfotransferases / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; C470791:SULF1 protein, human; D015238:Sulfotransferases