Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human LEC cells reveals KSHV manipulates notch signaling by upregulating Dll4 and JAG1 to alter cell cycle gene expression in

ABSTRACT: Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognizable by its distinctive red skin lesions. The lesions are KSHV infected spindle cells, most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. Here we examine KSHVs modulation of Notch signaling using wild-type LEC cells co-cultured with DLL4 and JAG1 expressing LEC cells. Experiment Overall Design: There are 1) n=2 of LEC control cells co-cultured with pSIN expressing LEC, 2) n=3 of LEC co-cultured with pSIN-Dll4 expressing LEC, and 3) n=3 of LEC co-cultured with pSIN-JAG1 expressing LEC.

ORGANISM(S): Homo sapiens

SUBMITTER: Stephen Henderson

PROVIDER: E-GEOD-16547 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description: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 (â?¥ 2 fold up/downregulation, p â?¤ 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. Experiment 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.

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Transcription profiling of human LEC cells reveals KSHV manipulates notch signaling by upregulating Dll4 and JAG1 to alter cell cycle gene expression in

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