Hsulf-1 Regulates Growth and Invasion of Pancreatic Cancer Cells

Overview

Journal J Clin Pathol

Specialty Pathology

Date 2006 Apr 11

PMID 16603650

Citations 16

Authors

I Abiatari

J Kleeff

J Li

K Felix

M W Buchler

H Friess

Affiliations

Soon will be listed here.

Abstract

Background: Hsulf-1 is a newly identified enzyme with arylsulphatase activity that can regulate the sulphation state of cell-surface heparan sulphate proteoglycans (HSPGs). In vitro overexpression of this enzyme in pancreatic cancer cells decreases responsiveness to fibroblastic growth factor-2, as Hsulf-1 is up regulated in primary pancreatic adenocarcinoma.

Aim: To further analyse the functions of the Hsulf-1 enzyme in vitro and in vivo with respect to growth, invasion and tumorigenicity.

Methods And Results: Transfection of Panc-1 pancreatic cancer cells with a full-length Hsulf-1 expression vector resulted in increased invasiveness and adhesiveness. An in vivo xenograft nude mouse tumour model showed a markedly reduced growth potential of Hsulf-1-expressing Panc-1 cells, which correlated with a considerably lower proliferation rate. Hsulf-1-positive nude mouse tumours showed better development of interstitial matrix structures, with increased blood vessel density in these tumours. In an orthotopic model, Hsulf-1-positive tumours exhibited enhanced local invasiveness. In human primary pancreatic cancers there was strong staining for sulphated HSPGs, which was markedly reduced in metastatic tissue samples.

Conclusion: Hsulf-1-mediated desulphation of HSPGs reduces the growth ability of Panc-1 pancreatic cancer cells, but increases the basal invasiveness of these cells, suggesting an important role of this enzyme in pancreatic cancer progression.

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References

Stanley M, Liebersbach B, Liu W, Anhalt D, Sanderson R . Heparan sulfate-mediated cell aggregation. Syndecans-1 and -4 mediate intercellular adhesion following their transfection into human B lymphoid cells. J Biol Chem. 1995; 270(10):5077-83. DOI: 10.1074/jbc.270.10.5077. View

Bernfield M, Gotte M, Park P, Reizes O, Fitzgerald M, Lincecum J . Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 2000; 68:729-77. DOI: 10.1146/annurev.biochem.68.1.729. View

Dai Y, Yang Y, MacLeod V, Yue X, Rapraeger A, Shriver Z . HSulf-1 and HSulf-2 are potent inhibitors of myeloma tumor growth in vivo. J Biol Chem. 2005; 280(48):40066-73. DOI: 10.1074/jbc.M508136200. View

Lai J, Chien J, Moser D, Staub J, Aderca I, Montoya D . hSulf1 Sulfatase promotes apoptosis of hepatocellular cancer cells by decreasing heparin-binding growth factor signaling. Gastroenterology. 2003; 126(1):231-48. DOI: 10.1053/j.gastro.2003.09.043. View

Fukuda K, Inui Y, Kawata S, Higashiyama S, Matsuda Y, Maeda Y . Increased mitogenic response to heparin-binding epidermal growth factor-like growth factor in vascular smooth muscle cells of diabetic rats. Arterioscler Thromb Vasc Biol. 1995; 15(10):1680-7. DOI: 10.1161/01.atv.15.10.1680. View

Lin X . Functions of heparan sulfate proteoglycans in cell signaling during development. Development. 2004; 131(24):6009-21. DOI: 10.1242/dev.01522. View

Kleeff J, Ishiwata T, Kumbasar A, Friess H, Buchler M, Lander A . The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer. J Clin Invest. 1998; 102(9):1662-73. PMC: 509114. DOI: 10.1172/JCI4105. View

Shlissel M, Berman B, Shaoul E, Admon A, Vlodavsky I, Carey D . Identification of glypican as a dual modulator of the biological activity of fibroblast growth factors. J Biol Chem. 1997; 272(19):12415-21. DOI: 10.1074/jbc.272.19.12415. View

LeBaron R, Hook A, Esko J, Gay S, Hook M . Binding of heparan sulfate to type V collagen. A mechanism of cell-substrate adhesion. J Biol Chem. 1989; 264(14):7950-6. View

10.

Jemal A, Murray T, Ward E, Samuels A, Tiwari R, Ghafoor A . Cancer statistics, 2005. CA Cancer J Clin. 2005; 55(1):10-30. DOI: 10.3322/canjclin.55.1.10. View

11.

David G . Integral membrane heparan sulfate proteoglycans. FASEB J. 1993; 7(11):1023-30. DOI: 10.1096/fasebj.7.11.8370471. View

12.

Sakata H, Stahl S, Taylor W, Rosenberg J, Sakaguchi K, Wingfield P . Heparin binding and oligomerization of hepatocyte growth factor/scatter factor isoforms. Heparan sulfate glycosaminoglycan requirement for Met binding and signaling. J Biol Chem. 1997; 272(14):9457-63. DOI: 10.1074/jbc.272.14.9457. View

13.

Li J, Kleeff J, Abiatari I, Kayed H, Giese N, Felix K . Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer. Mol Cancer. 2005; 4(1):14. PMC: 1087876. DOI: 10.1186/1476-4598-4-14. View

14.

Lai J, Chien J, Strome S, Staub J, Montoya D, Greene E . HSulf-1 modulates HGF-mediated tumor cell invasion and signaling in head and neck squamous carcinoma. Oncogene. 2004; 23(7):1439-47. DOI: 10.1038/sj.onc.1207258. View

15.

Lai J, Chien J, Staub J, Avula R, Greene E, Matthews T . Loss of HSulf-1 up-regulates heparin-binding growth factor signaling in cancer. J Biol Chem. 2003; 278(25):23107-17. DOI: 10.1074/jbc.M302203200. View

16.

Morimoto-Tomita M, Uchimura K, Werb Z, Hemmerich S, Rosen S . Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans. J Biol Chem. 2002; 277(51):49175-85. PMC: 2779716. DOI: 10.1074/jbc.M205131200. View

17.

Kleeff J, Wildi S, Kumbasar A, Friess H, Lander A, Korc M . Stable transfection of a glypican-1 antisense construct decreases tumorigenicity in PANC-1 pancreatic carcinoma cells. Pancreas. 1999; 19(3):281-8. DOI: 10.1097/00006676-199910000-00009. View

18.

Schluter C, Duchrow M, Wohlenberg C, BECKER M, Key G, Flad H . The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J Cell Biol. 1993; 123(3):513-22. PMC: 2200129. DOI: 10.1083/jcb.123.3.513. View

19.

Ozawa F, Friess H, Tempia-Caliera A, Kleeff J, Buchler M . Growth factors and their receptors in pancreatic cancer. Teratog Carcinog Mutagen. 2001; 21(1):27-44. DOI: 10.1002/1520-6866(2001)21:1<27::aid-tcm4>3.0.co;2-9. View

20.

Korc M . Role of growth factors in pancreatic cancer. Surg Oncol Clin N Am. 1998; 7(1):25-41. View