Unknown,Transcriptomics,Genomics,Proteomics

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VEGF189 overexpression in breast cancer cells delays metastasis

ABSTRACT: Vascular endothelial growth factor is a multifunctional cytokine playing important roles in angiogenesis, tumor progression and metastasis. Alternative splicing results in the production of several different isoforms of VEGF. We have previously generated human breast cancer cells overexpressing VEGF165 or VEGF189 isoforms (referred to as the V165 and V189 clones, respectively) and showed that VEGF189-transfected cells were less tumorigenic. In this study, we used bioluminescence imaging to analyze the metastasis capacity of breast cancer cell lines (MDA-MB-321) overexpressing VEGF isoforms in nude mice. V165, V189 and control cV clones were transfected with a luciferase plasmid to generate bioluminescent clones (the V165-B, V189-B and cV clones, respectively). These clones were then injected into the left heart ventricle of nude mice. Analysis of the location of metastases shows that V189-B cells induced fewer metastases in lung and bone than V165-B and cV-B cells. Moreover, there was a delay on metastasis appearance in mice receiving VEGF V189-B clone, consistent with increase survival in these mice. We investigated the possible mechanisms underlying these effects and found that VEGF189 increased adhesion and decreased cell invasion and survival in vitro. In the other side, transcriptomic analyses shown expression of genes, implicated in breast cancer and metastatic dissemination, in VEGF165 overexpressing cells. After in silico analyses of genes differentially expressed between V189 and V165 cells,we used Q-PCR assays to quantify mRNA levels of some gene of interest in 120 breast tumors from patients with or without metastasis and/or specially lung metastasis. We found that genes have prognostical significance and /or showed an influence on relapse-free survival. These data provide the first evidence that different VEGF isoforms have different effects on breast cancer cell line invasion and colonization. Human MDA-MB-231 breast cancer cells were used to generate stable transfected clones overexpressing VEGF165 isoform, VEGF189 isoform, or control vector (referred to as 42ctl8, 13ctl3 and PCIctl3, respectively). Analysis of the metastasis capacity of these clones in nude mice.

ORGANISM(S): Homo sapiens

SUBMITTER: toullec aurore

PROVIDER: E-GEOD-37911 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics.

Di Benedetto Melanie M Toullec Aurore A Buteau-Lozano Hélène H Abdelkarim Mohamed M Vacher Sophie S Velasco Guillaume G Christofari Monique M Pocard Marc M Bieche Ivan I Perrot-Applanat Martine M

British journal of cancer 20150721 5

<h4>Background</h4>Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that has important roles in angiogenesis. Our knowledge of the significance of VEGF isoforms in human cancer remains incomplete.<h4>Methods</h4>Bioluminescence imaging and transcriptomic analysis were used to study the colonisation capacity of the human breast cancer cells MDA-MB-231 controlling or overexpressing the VEGF165 or VEGF189 isoform (named cV-B, V165-B and V189-B, respectively) in nude mice.<h4> ...[more]

PMID: 26196186

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Dataset Information

VEGF189 overexpression in breast cancer cells delays metastasis

Publications

MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics.

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