MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics.
Br J Cancer, 2015/9/01;113(5):773-85.
Di Benedetto M[1, 2], Toullec A[3, 4, 5], Buteau-Lozano H[3, 4, 5], Abdelkarim M[1, 2], Vacher S[6], Velasco G[3, 4, 5], Christofari M[3, 4, 5], Pocard M[3, 4, 5], Bieche I[6], Perrot-Applanat M[3, 4, 5]
Affiliations
PMID: 26196186DOI: 10.1038/bjc.2015.267
Impact factor: 9.075
Abstract
background: 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.
methods: 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.
results: When injected into the bloodstream, V189-B cells induced less metastasis in the lungs and bone than V165-B and cV-B control cells, consistent with longer survival of these mice and delay in tumour uptake in the mice injected with a V189-B clone. Histological analysis confirmed that there were less αSMA-positive cells in the lungs of the mice injected with V189-B. In vitro V189-B cells decreased both cell invasion and survival. Using transcriptomic analysis, we identified a subset of 18 genes expressed differentially between V189 and V165 cell lines and in 120 human breast tumours. V165 was associated with poor prognosis, whereas V189 was not, suggesting a complex regulation by VEGF isoforms. Our results showed a negative correlation between the expression pattern of VEGF189 and the levels of expression of seven genes that influence metastasis.
conclusion: Our findings provide the first evidence that VEGF isoforms have different effects on breast cancer cell line colonisation in vivo.
MeSH terms
Animals; Area Under Curve; Autocrine Communication; Bone Neoplasms; Breast Neoplasms; Cell Line, Tumor; Female; Humans; Lung Neoplasms; Mice, Nude; Middle Aged; Neoplasm Transplantation; Neuropilin-1; Protein Isoforms; Transcriptome; Vascular Endothelial Growth Factor A
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