Source:http://linkedlifedata.com/resource/pubmed/id/19431209
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2009-7-21
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| pubmed:abstractText |
Angiogenesis is essential for tumor growth and metastasis. Although ELR(+)-CXC-chemokines and their corresponding receptor, CXC-receptor 2 (CXCR2), are known mediators of angiogenesis, little is known about their role in pancreatic cancer (PaCa). The aim of our study was to determine the role of ELR(+)-CXC-chemokine/CXCR2 biological axis in promoting PaCa angiogenesis. We prospectively collected secretin-stimulated exocrine pancreatic secretions (SSEPS) from normal individuals (NP) and PaCa patients. We showed that summed concentrations of ELR(+)-CXC-chemokines in SSEPS from PaCa patients were significantly higher than in those from NP (p = 0.002). We measured ELR(+)-CXC-chemokine levels in supernatants from multiple PaCa cell lines and confirmed that BxPC-3, Colo-357 and Panc-28 had significantly higher expression compared with an immortalized human pancreatic ductal epithelial (HPDE) cell line. After confirming lack of autocrine effects of ELR(+)-CXC-chemokines on PaCa cells (due to absence of CXCR2 expression), we investigated paracrine effects of these chemokines on human umbilical vein endothelial cells (HUVEC). Both recombinant ELR(+)-CXC-chemokines and co-culturing with BxPC-3 significantly enhanced proliferation, invasion, and tube formation of HUVEC (p < 0.05). These biological effects were significantly inhibited by treatment with a neutralizing antibody against CXCR2 (anti-CXCR2 Ab) (p < 0.05). Finally, anti-CXCR2 Ab significantly reduced tumor volume (p < 0.05), Ki-67 proliferation index (p = 0.043) and Factor VIII(+) microvessel density (p = 0.004) in an orthotopic nude mouse PaCa model. Our results show that ELR(+)-CXC-chemokines promote PaCa tumor-associated angiogenesis through CXCR2, suggesting that CXCR2 is an anti-angiogenic target in PaCa.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-8B,
http://linkedlifedata.com/resource/pubmed/chemical/Secretin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
|
| pubmed:issn |
1097-0215
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| pubmed:author |
pubmed-author:BurdickMarie DMD,
pubmed-author:GillKanwar RKR,
pubmed-author:GuhaSushovanS,
pubmed-author:HoffmanRobert MRM,
pubmed-author:MatsuoYoichiY,
pubmed-author:RaimondoMassimoM,
pubmed-author:StrieterRobert MRM,
pubmed-author:TongZhiminZ,
pubmed-author:WallaceMichael BMB,
pubmed-author:WoodwardTimothy ATA,
pubmed-author:YangZhijianZ
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| pubmed:copyrightInfo |
2009 UICC.
|
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
125
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1027-37
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| pubmed:meshHeading |
pubmed-meshheading:19431209-Adolescent,
pubmed-meshheading:19431209-Animals,
pubmed-meshheading:19431209-Blotting, Western,
pubmed-meshheading:19431209-Cell Proliferation,
pubmed-meshheading:19431209-Cells, Cultured,
pubmed-meshheading:19431209-Chemokines, CXC,
pubmed-meshheading:19431209-Endothelium, Vascular,
pubmed-meshheading:19431209-Humans,
pubmed-meshheading:19431209-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:19431209-Male,
pubmed-meshheading:19431209-Mice,
pubmed-meshheading:19431209-Mice, Nude,
pubmed-meshheading:19431209-Neovascularization, Pathologic,
pubmed-meshheading:19431209-Pancreatic Neoplasms,
pubmed-meshheading:19431209-Pilot Projects,
pubmed-meshheading:19431209-Prospective Studies,
pubmed-meshheading:19431209-RNA, Messenger,
pubmed-meshheading:19431209-Receptors, Interleukin-8B,
pubmed-meshheading:19431209-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19431209-Secretin,
pubmed-meshheading:19431209-Umbilical Veins
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| pubmed:year |
2009
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| pubmed:articleTitle |
CXC-chemokine/CXCR2 biological axis promotes angiogenesis in vitro and in vivo in pancreatic cancer.
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| pubmed:affiliation |
Department of Gastroenterology, Hepatology and Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA.
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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