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[Cancer Research 61, 4655-4659, June 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Heparanase Expression in Primary and Metastatic Pancreatic Cancer1

Alexander Koliopanos, Helmut Friess2, Jörg Kleeff, Xin Shi, Quan Liao, Iris Pecker, Israel Vlodavsky, Arthur Zimmermann and Markus W. Büchler

Department of Visceral and Transplantation Surgery [A. K., H. F., J. K., X. S., Q. L., M. W. B.] and Institute of Pathology [A. Z.], University of Bern, Inselspital, CH-3010 Bern, Switzerland, Department of Molecular Biology, Insight Ltd., Rehovo 76121, Israel [I. P.] and Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel [I. V.]

The human endoglycosidase heparanase (hpa) degrades heparan-sulfate proteoglycans, which constitute prominent components of basement membranes and extracellular matrix. Due to the critical function of hpa in cancer cell invasion and metastasis, we have analyzed the expression of hpa in human primary and metastatic pancreatic cancer as well as in the normal pancreas and in chronic pancreatic inflammation. By real-time quantitative PCR, there was a 7.9- and 30.2-fold increase of hpa mRNA in chronic pancreatitis and pancreatic cancer tissue samples, respectively, in comparison with normal pancreatic tissues. There was a significant correlation between enhanced hpa mRNA expression and shorter postoperative patient survival. hpa mRNA and protein localized in the cancer cells of primary and metastatic pancreatic cancer, with a preferentially higher expression at the primary tumor site. Cultured pancreatic cancer cells transfected with a full-length hpa construct displayed enhanced invasiveness in an invasion chamber assay. These results suggest that hpa overexpression in human pancreatic cancers facilitates cancer cell invasion, thereby enhancing the metastatic potential of the tumors.




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