The human endoglycosidase heparanase (hpa) degrades heparan-sulfate proteog
lycans, which constitute prominent components of basement membranes and ext
racellular matrix. Due to the critical function of hpa in cancer cell invas
ion 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 pancre
atic cancer tissue samples, respectively, in comparison with normal pancrea
tic 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. Culture
d pancreatic cancer cells transfected with a full-length hpa construct disp
layed enhanced invasiveness in an invasion chamber assay. These results sug
gest that hpa overexpression in human pancreatic cancers facilitates cancer
cell invasion, thereby enhancing the metastatic potential of the tumors.