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


CONCLUSIONS
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.
Li
Junsheng
J
Department of General Surgery, University of Heidelberg, Heidelberg, Germany. lijunsheng70@hotmail.com
Kleeff
Jörg
J
Abiatari
Ivane
I
Kayed
Hany
H
Giese
Nathalia A
NA
Felix
Klaus
K
Giese
Thomas
T
Büchler
Markus W
MW
Friess
Helmut
H
D000328:Adult; D000368:Aged; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D010179:Pancreas / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D013429:Sulfatases / Q000235:genetics; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; C470791:SULF1 protein, human; D015238:Sulfotransferases; D013429:Sulfatases