%0 Journal Article
%T Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer
%A Junsheng Li
%A J£¿rg Kleeff
%A Ivane Abiatari
%A Hany Kayed
%A Nathalia A Giese
%A Klaus Felix
%A Thomas Giese
%A Markus W B¨¹chler
%A Helmut Friess
%J Molecular Cancer
%D 2005
%I BioMed Central
%R 10.1186/1476-4598-4-14
%X Pancreatic cancer samples expressed significantly (22.5-fold) increased Hsulf-1 mRNA levels compared to normal controls, and Hsulf-1 mRNA was localized in the cancer cells themselves as well as in peritumoral fibroblasts. 4 out of 8 examined pancreatic cancer cell lines expressed Hsulf-1, whereas its expression was below the level of detection in the other cell lines. Stable transfection of the Hsulf-1 negative Panc-1 pancreatic cancer cell line with a full length Hsulf-1 expression vector resulted in increased sulfatase activity and decreased cell-surface heparan-sulfate proteoglycan (HSPG) sulfation. Hsulf-1 expression reduced both anchorage-dependent and -independent cell growth and decreased FGF-2 mediated cell growth and invasion in this cell line.High expression of Hsulf-1 occurs in the stromal elements as well as in the tumor cells in pancreatic cancer and interferes with heparin-binding growth factor signaling.Pancreatic cancer is one of the most aggressive human malignancies with an overall five-year survival rate of less then 5% [1]. Although the reasons for the aggressive growth behavior of pancreatic cancer are not completely understood, recent molecular biological studies have revealed several factors that are involved in the pathogenesis of pancreatic cancer. These include genetic changes, such as k-ras, p53, p16, and Smad4 mutations [2], as well as epigenetic alterations, such as overexpression of a number of growth factors and their receptors [3,4].Membrane-associated heparin-sulfate proteoglycans (HSPGs) are thought to play an important role in many aspects of cellular physiology including growth factor signaling. HSPGs are required for the optimal activity of heparin-binding growth factors, such as for example fibroblast growth factors (FGFs) [5,6]. One member of the HSPG family, glypican-1 is over-expressed in pancreatic cancer and influences heparin binding growth factor signaling in this disease [7,8]. The heparan-sulfate (HS) chains of HSPGs se
%K pancreatic cancer
%K growth factors
%K sulfatase
%K proteoglycans
%U http://www.molecular-cancer.com/content/4/1/14