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

Li Junsheng, Kleeff Jörg, Abiatari Ivane, Kayed Hany, Giese, Felix Klaus, Giese Thomas, Büchler, Friess, Friess Helmut

Description

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.

Sujets

• Pancreatic cancer
• Growth factor
• Sulfatase
• Proteoglycan

Informations

• Publié par: biomed
• Publié le: 01 janvier 2005
• Nombre de lectures: 5
• Langue: English

Extrait

Pga e 1fo1  ( 4 apegum nr bet nor foaticnoitrup esops)

Introduction understood, recent molecular biological studies have Pancreatic cancer is one of the most aggressive human revealed several factors that are involved in the pathogen- malignancies with an overall five-year survival rate of less esis of pancreatic cancer. These include genetic changes, then 5% [1]. Although the reasons for the aggressive such as k-ras, p53, p16, and Smad4 mutations [2], as well growth behavior of pancreatic cancer are not completely

Bio Med  Central

Research Open Access Enhanced levels of Hs ulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer Junsheng Li 1,2 , Jörg Kleeff* 1 , Ivane Abiatari 1 , Hany Kayed 1 , Nathalia A Giese 1 , Klaus Felix 1 , Thomas Giese 3 , Markus W Büchler 1 and Helmut Friess 1

Address: 1 Department of General Surgery, Universi ty of Heidelberg, Heidelberg, Germany, 2 Department of General Su rgery, Zhong-Da Hospital, Southeast University, Nanjing, China and 3 Institute of Immunology, University of Heidelberg, Heidelberg, Germany Email: Junsheng Li - lijunsheng70@ho tmail.com; Jörg Kleeff* - joerg_kle [e-mail]; Ivan e Abiatari - [e-mail]- heidelberg.de; Hany Kayed - hany_ ayed@m ed.uni-heidelberg.de; Nathalia A Giese - [e-mail]; k us Felix - [e-mail]; Thoma _g [e-mail]; Kla s Giese - thomas i Markus W Büchler - [e-mail]; Helmut Friess - [e-mail] * Corresponding author

Published: 07 April 2005 Received: 28 March 2005 Molecular Cancer 2005, 4 :14 doi:10.1186/1476-4598-4-14  Accepted: 07 April 2005 This article is available from: http:/ /www.molecular-cancer.com/content/4/1/14 © 2005 Li et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the orig inal work is properly cited.

Molecular Cancer

Abstract Hsulf-1 is a newly identified enzy me, which has the ability to decrea se the growth of hepatocellular, ovarian, and head and neck squamous cell carc inoma cells by interfering with heparin-binding growth factor signaling. Since pancreatic cancer s over-express a number of heparin-binding growth factors and their receptors, the e xpression and function of this enzyme in pancreatic cancer was analyzed. Results: Pancreatic cancer samples expressed signif icantly (22.5-fold) increased Hsulf-1 mRNA levels compared to normal co ntrols, and Hsulf-1 mRNA was lo calized 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 belo w the level of detection in the other cell lines. Stable transfection of the Hsulf-1 negative Panc-1 panc reatic cancer cell line with a full length Hsulf- 1 expression vector resulted in increased sulfatase activity and decreased cell-surface heparan- sulfate proteoglycan (HSPG) sulfat ion. Hsulf-1 expression reduced both anchorage-dependent and -independent cell growth and decreased FGF-2 mediat ed 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.

pancreatic cancergrowth fa ctorssulfataseproteoglycans