Linked Life Data

7533661

Source:http://linkedlifedata.com/resource/pubmed/id/7533661

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1995-4-12
pubmed:abstractText
Capillary hemangioblastoma is the most frequent manifestation of the autosomal dominantly inherited von Hippel-Lindau (VHL) disease but also presents as a nonfamilial, sporadic vascular tumor. Hemangioblastomas are characterized by a dense network of capillaries in association with cysts. To investigate the mechanisms underlying neovascularization and cyst formation, we analyzed eight VHL disease-associated and five sporadic hemangioblastomas. Histologically, both tumor types showed a similar phenotype. The capillaries expressed the endothelial cell markers von Willebrand factor and CD31 antigen. We investigated the expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen which is also known to induce vascular permeability in vivo, and its high affinity tyrosine kinase receptors flt-1 and KDR. Northern blot and in situ hybridization analysis revealed significant up-regulation of VEGF and VEGF receptor expression in VHL disease-associated and sporadic hemangioblastomas compared to normal brain and tumor stromal cells as sites of abundant VEGF transcription. Endothelial cells did not express detectable amounts of VEGF mRNA but coexpressed flt-1 and KDR. By immunohistochemistry, VEGF protein was detectable in the tumor interstitium and was found to be concentrated around capillaries. Performing reverse transcription-PCR, we demonstrated that VEGF121 and VEGF165 were the splice variants predominantly expressed, whereas mRNA encoding VEGF189 was present at smaller amounts. Our findings suggest that, in VHL disease-associated and sporadic hemangioblastomas, VEGF121 and VEGF165 are secreted by stromal cells and interact with the corresponding VEGF receptors expressed on tumor endothelial cells. This paracrine mechanism may mediate neovascularization and cyst formation in capillary hemangioblastomas.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1358-64
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7533661-Adult, pubmed-meshheading:7533661-Base Sequence, pubmed-meshheading:7533661-Endothelial Growth Factors, pubmed-meshheading:7533661-Female, pubmed-meshheading:7533661-Genes, Tumor Suppressor, pubmed-meshheading:7533661-Hemangioblastoma, pubmed-meshheading:7533661-Humans, pubmed-meshheading:7533661-Lymphokines, pubmed-meshheading:7533661-Male, pubmed-meshheading:7533661-Middle Aged, pubmed-meshheading:7533661-Molecular Sequence Data, pubmed-meshheading:7533661-Neovascularization, Pathologic, pubmed-meshheading:7533661-RNA, Messenger, pubmed-meshheading:7533661-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:7533661-Receptors, Growth Factor, pubmed-meshheading:7533661-Receptors, Vascular Endothelial Growth Factor, pubmed-meshheading:7533661-Up-Regulation, pubmed-meshheading:7533661-Vascular Endothelial Growth Factor A, pubmed-meshheading:7533661-Vascular Endothelial Growth Factors, pubmed-meshheading:7533661-von Hippel-Lindau Disease
pubmed:year
1995
pubmed:articleTitle
Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas.
pubmed:affiliation
Max-Planck-Institut für physiologische und klinische Forschung, W.G. Kerckhoff-Institut, Abteilung Molekulare Zellbiologie, Bad Nauheim, Germany.
pubmed:publicationType
Journal Article