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    <creators>
      <item>
        <name>
          <family>Abiatari</family>
          <given>Ivane</given>
        </name>
        <id>ivane.abiatari@iliauni.edu.ge</id>
      </item>
      <item>
        <name>
          <family>Kleeff</family>
          <given>J</given>
        </name>
      </item>
      <item>
        <name>
          <family>Li</family>
          <given>J</given>
        </name>
      </item>
      <item>
        <name>
          <family>Felix</family>
          <given>K</given>
        </name>
      </item>
      <item>
        <name>
          <family>Büchler</family>
          <given>M W</given>
        </name>
      </item>
      <item>
        <name>
          <family>Friess</family>
          <given>H</given>
        </name>
      </item>
    </creators>
    <title>Hsulf-1 regulates growth and invasion of pancreatic cancer cells.</title>
    <ispublished>pub</ispublished>
    <subjects>
      <item>RC0254</item>
    </subjects>
    <full_text_status>public</full_text_status>
    <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.</abstract>
    <date>2006-10</date>
    <date_type>published</date_type>
    <publication>Journal of clinical pathology</publication>
    <volume>59</volume>
    <number>10</number>
    <pagerange>1052-8</pagerange>
    <refereed>TRUE</refereed>
    <issn>0021-9746</issn>
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