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Series GSE6255 Query DataSets for GSE6255
Status Public on Sep 22, 2008
Title Lymphatic endothelium of metastatic tumours has a distinct transcription profile.
Organism Mus musculus
Experiment type Expression profiling by array
Summary Invasion of lymphatic vessels is a key step in the metastasis of primary tumour cells to draining lymph nodes. Recent evidence indicates that such metastasis can be facilitated by tumour lymphangiogenesis, although it remains unclear whether this is a consequence of increased lymphatic vessel numbers or alteration in the properties of the vessels themselves. Here we have addressed this important question by comparing the RNA profile of normal dermal lymphatic endothelial cells (LEC) with those isolated from tumours of murine T-241/VEGF-C metastatic fibrosarcoma. Our findings reveal significant changes in the expression of some 792 genes in tumour lymphatics (≥ 2 fold up/downregulation, p ≤ 0.05), involving particularly transcripts associated with junctional adhesion, immunomodulation, extracellular matrix and vessel growth/patterning, several of which we have confirmed by RT-PCR and/or immunohistochemistry. Interestingly, this altered phenotype could not be attributed solely to VEGF-C induced lymphoproliferation, as no similar change in gene expression was reported when human LEC were cultured with VEGF-C in vitro. Moreover, we show that a key protein upregulated in the mouse model, namely the tight junction protein Endothelial Cell Specific Adhesion Molecule (ESAM), is similarly upregulated in tumour lymphatic vessels from 2/2 patients with head and neck squamous cell carcinoma and 4/4 patients with aggressive bladder carcinoma. These findings demonstrate a previously unrecognized influence of tumour environment on lymphatic gene expression and identify candidate tumour specific vessel markers that may prove valuable for either prognosis or therapy.
Keywords: Tumor, Metastasis, Lymphatic endothelium, comparative transcriptional profiling
 
Overall design Here we have investigated the invasion of lymphatic vessels as a key step in the metastasis of primary tumour cells to draining lymph nodes by comparing the gene expression profile of normal dermal lymphatic endothelial cells (LEC) with those isolated from tumours of murine T241/VEGF-C/GFP metastatic fibrosarcoma. Three biological replicates were analyzed from each group.
 
Contributor(s) Clasper S, Baban D, Cao Y, Ewers S, Butz S, Vestweber D, Jackson DG
Citation(s) 18794116
Submission date Nov 09, 2006
Last update date Feb 11, 2019
Contact name Dilair Baban
E-mail(s) dilair.baban@well.ox.ac.uk
Phone +44(0)1865287521
Organization name University of Oxford
Department Wellcome Trust Centre Human Genetics
Lab Genomics
Street address Roosevelt Drive
City Oxford
ZIP/Postal code OX3 7BN
Country United Kingdom
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (6)
GSM143691 Murine fibrosarcoma tumor cells_rep 2
GSM143692 Murine fibrosarcoma tumor cells_rep 3
GSM143917 Murine fibrosarcoma tumor cells_rep 1
Relations
BioProject PRJNA99687

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE6255_RAW.tar 36.1 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file

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