Linked Life Data

15548713

Source:http://linkedlifedata.com/resource/pubmed/id/15548713

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2004-11-19
pubmed:abstractText
In this study, we have evaluated 11 pancreatic tumor cell lines and tumor cells from surgical samples of patients with pancreatic adenocarcinoma for expression of the chemokine receptor CXCR4. Six of 11 cell lines expressed detectable mRNA of CXCR4, with three cell lines (AsPC1, Capan1, and Hs766T) having substantial amounts of transcripts. Expression was higher in lines derived from metastatic lesions compared with those derived from primary tumors. Different inflammatory cytokines did not modify expression, whereas IFN-gamma down-regulated and hypoxia up-regulated CXCR4 transcripts. Transcript expression was associated with surface expression in pancreatic carcinoma cell lines. All surgical carcinoma samples tested expressed higher levels of CXCR4 than normal pancreatic ducts, which were used as reference tissue. The chemokine CXCL12 induced chemotaxis in CXCR4-positive pancreatic carcinoma cell lines, which was inhibited by anti-CXCR4 monoclonal antibody and by the antagonist AMD3100. Transendothelial migration, Matrigel invasion, and activation of matrix metalloproteases were also enhanced by CXCL12. In CXCR4-positive cell lines, CXCL12 stimulated cell proliferation. The cell line Hs766T produces high levels of CXCL12, and addition of the CXCR4 antagonist AMD3100 partially inhibited proliferation, indicating an autocrine loop. Moreover, the addition of exogenous CXCL12 inhibited apoptosis induced by serum starvation. These results indicate that the CXCR4 receptor is frequently expressed in metastatic pancreatic tumor cells. CXCR4 not only stimulates cell motility and invasion but also promotes survival and proliferation. Strategies to target CXCR4 expressed on tumor cells may be of benefit in patients with pancreatic cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8420-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4.
pubmed:affiliation
Department of Immunology and Cell Biology, Mario Negri Institute, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't