Research

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

Junsheng Li^1,2 , Jörg Kleeff¹ , Ivane Abiatari¹ , Hany Kayed¹ , Nathalia A Giese¹ , Klaus Felix¹ , Thomas Giese³ , Markus W Büchler¹ and Helmut Friess¹

¹  Department of General Surgery, University of Heidelberg, Heidelberg, Germany

²  Department of General Surgery, Zhong-Da Hospital, Southeast University, Nanjing, China

³  Institute of Immunology, University of Heidelberg, Heidelberg, Germany

author email corresponding author email

Molecular Cancer 2005, 4:14doi:10.1186/1476-4598-4-14

Published:	7 April 2005

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.