Plasmalemmal vesicle associated protein-1 is a novel marker implicated in brain tumor angiogenesis.
OBJECTIVE
Plasmalemmal vesicle associated protein-1 (PV-1) is up-regulated in the endothelium of human glioblastoma. We sought to further characterize the expression pattern of PV-1 in human brain tumors and interrogate its role in brain tumor angiogenesis.


METHODS
Quantitative reverse transcription-PCR and in situ hybridization were used to measure PV-1 expression in a panel of 46 human brain tumors and related pathologic states. Matrigel tubulogenesis assays and cell migration assays were used to show function of PV-1 in primary human endothelial cells (HMVEC) under gene knockdown conditions.


RESULTS
PV-1 is selectively up-regulated in a variety of high-grade human brain tumors, including glioblastoma and metastatic carcinoma, as well as other cerebral disorders associated with blood-brain barrier disruption, such as acute ischemia. Expression levels were reduced in low-grade neoplasia; however, tumors associated with the ependyma and choroid plexus, known sites of PV-1 expression, also exhibited robust expression. Cerebral expression of PV-1 mRNA was confined to endothelial cells in all cases. PV-1 expression was induced in HMVEC cells in vitro by exposure to medium conditioned by U87MG and U251MG human brain tumor cell lines and by medium supplemented with exogenous vascular endothelial growth factor or scatter factor/hepatocyte growth factor. RNA interference-mediated inhibition of PV-1 induction in HMVEC cells blocked Matrigel-induced tubulogenesis and inhibited cell migration induced by conditioned medium or angiogenic growth factors.


CONCLUSIONS
Our results confirm that PV-1 is preferentially induced in the endothelium of high-grade human brain tumors. Inhibition of PV-1 expression is associated with failure of endothelial differentiation in vitro. PV-1 represents a novel marker of brain tumor angiogenesis and integrity of the blood-brain barrier and is a potential therapeutic target.
Carson-Walter
Eleanor B
EB
Department of Neurosurgery, University of Pittsburgh, PA 15213, USA.
Hampton
Jessica
J
Shue
Eveline
E
Geynisman
Daniel M
DM
Pillai
Pramod Kumar
PK
Sathanoori
Ramasri
R
Madden
Stephen L
SL
Hamilton
Ronald L
RL
Walter
Kevin A
KA
D014408:Biomarkers, Tumor; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D007511:Ischemia; D007797:Laminin / Q000737:chemistry; D008565:Membrane Proteins / Q000096:biosynthesis*; D008833:Microcirculation; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011509:Proteoglycans / Q000737:chemistry; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007797:Laminin; D008565:Membrane Proteins; C486771:PLVAP protein, human; D011509:Proteoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D012313:RNA; D003094:Collagen