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Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer

Author(s): Li Junsheng | Kleeff Jörg | Abiatari Ivane | Kayed Hany | Giese Nathalia | Felix Klaus | Giese Thomas | Büchler Markus | Friess Helmut

Journal: Molecular Cancer
ISSN 1476-4598

Volume: 4;
Issue: 1;
Start page: 14;
Date: 2005;
Original page

Keywords: pancreatic cancer | growth factors | sulfatase | proteoglycans

Abstract Hsulf-1 is a newly identified enzyme, which has the ability to decrease the growth of hepatocellular, ovarian, and head and neck squamous cell carcinoma cells by interfering with heparin-binding growth factor signaling. Since pancreatic cancers over-express a number of heparin-binding growth factors and their receptors, the expression and function of this enzyme in pancreatic cancer was analyzed. Results 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. Conclusion 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.

Tango Jona
Tangokurs Rapperswil-Jona

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