2209 9 9648 1 26785 document 9648 1476-4598-4-14.pdf application/pdf e4bd0b24a49d99e9a39410629b40598f MD5 889736 2015-04-29 13:26:46 http://eprints.iliauni.edu.ge/2209/1/1476-4598-4-14.pdf 2209 1 1 application/pdf text en public

1476-4598-4-14.pdf

archive 207 disk0/00/00/22/09 2015-04-30 05:29:07 2015-04-30 05:29:07 2015-04-30 05:29:07 article show Li Junsheng Kleeff Jörg Abiatari Ivane ivane.abiatari@iliauni.edu.ge Kayed Hany Giese Nathalia A Felix Klaus Giese Thomas Büchler Markus W Friess Helmut pub R1 public UNLABELLED 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. 2005 published Molecular cancer 4 1 14 TRUE 1476-4598