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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1998-3-9
pubmed:abstractText
Plasminogen activators (PAs) play an important role in tumor cell invasion. We have analysed the expression of tissue-type PA (t-PA), urokinase-type PA (u-PA), and their respective receptors, annexin II and u-PAR, in normal and neoplastic cultures of pancreatic cells, as well as in pancreatic tissues, and have examined their role in tumor invasiveness in vitro. Using Northern blotting, Western blotting, and ELISA, t-PA is detected in cultured pancreas cancer cells displaying a well differentiated phenotype but it is undetectable in less differentiated cells and in normal pancreatic cultures. In contrast, u-PA transcripts, protein, and enzymatic activity are detected both in cancer cells and in normal cultures. Higher levels of u-PAR and annexin II are present in cancer cells than in normal cultures and, in SK-PC-1 cells, both receptors are localized in the basolateral membrane. In vitro invasion assays indicate that both t-PA and u-PA contribute to the invasiveness of SK-PC-1 cells through reconstituted extracellular matrix. To determine the relevance of these studies to pancreas cancer, immunohistochemical assays have been used to examine the expression of t-PA, u-PA, and their receptors in normal and neoplastic tissues. t-PA is absent from normal pancreas and from tumor associated pancreatitis, whereas it is detected in the majority of pancreas cancer tissues (16/17). Annexin II is also overexpressed in some tumors (5/13). u-PAR is overexpressed in most tumor samples examined (14/15), while u-PA is weakly detected in a low number of cases (3/14); both u-PAR and u-PA are overexpressed in areas of tumor associated pancreatitis. Indirect evidences indicate that K-ras and p53 mutated proteins can regulate the expression of PAs. In pancreatic cancer we have found an association between codon 12 K-ras mutations and t-PA expression (P=0.04). These results support the contention that, in the exocrine pancreas, activation of t-PA is more specifically associated to neoplastic transformation and to the invasive phenotype, whereas the induction of u-PA/u-PAR system might be more relevant to inflammatory or non-neoplastic events.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
625-33
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
The plasminogen activator system in pancreas cancer: role of t-PA in the invasive potential in vitro.
pubmed:affiliation
Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't