Source:http://linkedlifedata.com/resource/pubmed/id/21385870
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
17
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pubmed:dateCreated |
2011-4-25
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pubmed:abstractText |
Glioblastoma is one of the most fatal cancers, characterized by a strong vascularized phenotype. YKL-40, a secreted glycoprotein, is overexpressed in patients with glioblastomas and has potential as a novel tumor biomarker. The molecular mechanisms of YKL-40 in glioblastoma development, however, are poorly understood. Here, we aimed to elucidate the role YKL-40 plays in the regulation of VEGF expression, tumor angiogenesis, and radioresistance. YKL-40 up-regulated VEGF expression in glioblastoma cell line U87, and both YKL-40 and VEGF synergistically promote endothelial cell angiogenesis. Interestingly, long term inhibition of VEGF up-regulated YKL-40. YKL-40 induced coordination of membrane receptor syndecan-1 and integrin ?v?5, and triggered a signaling cascade through FAK(397) to ERK-1 and ERK-2, leading to elevated VEGF and enhanced angiogenesis. In addition, ?-irradiation of U87 cells increased YKL-40 expression that protects cell death through AKT activation and also enhances endothelial cell angiogenesis. Blockade of YKL-40 activity or expression decreased tumor growth, angiogenesis, and metastasis in xenografted animals. Immunohistochemical analysis of human glioblastomas revealed a correlation between YKL-40, VEGF, and patient survival. These findings have shed light on the mechanisms by which YKL-40 promotes tumor angiogenesis and malignancy, and thus provide a therapeutic target for tumor treatment.
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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/Adipokines,
http://linkedlifedata.com/resource/pubmed/chemical/CHI3L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1083-351X
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
29
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15332-43
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21385870-Adipokines,
pubmed-meshheading:21385870-Animals,
pubmed-meshheading:21385870-Cell Line, Tumor,
pubmed-meshheading:21385870-Disease Progression,
pubmed-meshheading:21385870-Gamma Rays,
pubmed-meshheading:21385870-Glioblastoma,
pubmed-meshheading:21385870-Glycoproteins,
pubmed-meshheading:21385870-Humans,
pubmed-meshheading:21385870-Lectins,
pubmed-meshheading:21385870-Neoplasm Metastasis,
pubmed-meshheading:21385870-Neoplasms, Experimental,
pubmed-meshheading:21385870-Neovascularization, Pathologic,
pubmed-meshheading:21385870-Survival Rate,
pubmed-meshheading:21385870-Transplantation, Heterologous,
pubmed-meshheading:21385870-Vascular Endothelial Growth Factor A
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pubmed:year |
2011
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pubmed:articleTitle |
Role of YKL-40 in the angiogenesis, radioresistance, and progression of glioblastoma.
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pubmed:affiliation |
Molecular and Cellular Biology Program, Morrill Science Center, University of Massachusetts, Amherst, Massachusetts 01003, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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