title: MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics.
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.
  
  
  CONCLUSIONS
  Our findings provide the first evidence that VEGF isoforms have different effects on breast cancer cell line colonisation in vivo.
authors.affiliation: Université Paris 13, A Avenue JB Clément, Villetaneuse, Paris, France.|INSERM UMR1165 Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France.
authors.forename: Melanie
authors.initials: M
authors.lastname: Di Benedetto
authors.affiliation: INSERM U965, Hôpital Lariboisière-Saint Louis, 75010 Paris, France.|Université Paris-Diderot, 41 boulevard de la Chapelle, 75475 Paris, France.|University of Paris VII, Paris, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Toullec
authors.affiliation: INSERM U965, Hôpital Lariboisière-Saint Louis, 75010 Paris, France.|Université Paris-Diderot, 41 boulevard de la Chapelle, 75475 Paris, France.|University of Paris VII, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Buteau-Lozano
authors.affiliation: Université Paris 13, A Avenue JB Clément, Villetaneuse, Paris, France.|INSERM UMR1165 Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdelkarim
authors.affiliation: Unité de Pharmacogénomique, Service de Génétique, Institut Curie, 26 rue d'Ulm, 75248 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vacher
authors.affiliation: INSERM U965, Hôpital Lariboisière-Saint Louis, 75010 Paris, France.|Université Paris-Diderot, 41 boulevard de la Chapelle, 75475 Paris, France.|University of Paris VII, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Velasco
authors.affiliation: INSERM U965, Hôpital Lariboisière-Saint Louis, 75010 Paris, France.|Université Paris-Diderot, 41 boulevard de la Chapelle, 75475 Paris, France.|University of Paris VII, Paris, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Christofari
authors.affiliation: INSERM U965, Hôpital Lariboisière-Saint Louis, 75010 Paris, France.|Université Paris-Diderot, 41 boulevard de la Chapelle, 75475 Paris, France.|University of Paris VII, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Pocard
authors.affiliation: Unité de Pharmacogénomique, Service de Génétique, Institut Curie, 26 rue d'Ulm, 75248 Paris, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
authors.affiliation: INSERM U965, Hôpital Lariboisière-Saint Louis, 75010 Paris, France.|Université Paris-Diderot, 41 boulevard de la Chapelle, 75475 Paris, France.|University of Paris VII, Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Perrot-Applanat
mesh_terms: D000818:Animals; D019540:Area Under Curve; D019898:Autocrine Communication; D001859:Bone Neoplasms / Q000378:metabolism* / Q000556:secondary; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D039942:Neuropilin-1 / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D059467:Transcriptome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1