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

• Main Authors: Giese Nathalia A, Kayed Hany, Abiatari Ivane, Kleeff Jörg, Li Junsheng, Felix Klaus, Giese Thomas, Büchler Markus W, Friess Helmut
• Format: Article
• Language: English
• Published: BMC 2005-04-01
• Series: Molecular Cancer
• Subjects: pancreatic cancer; growth factors; sulfatase; proteoglycans
• Online Access: http://www.molecular-cancer.com/content/4/1/14

<p>Abstract</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>