title: High expression levels of egfl7 correlate with low endothelial cell activation in peritumoral vessels of human breast cancer.
abstract: Tumor blood vessels participate in the immune response against cancer cells and we previously used pre-clinical models to demonstrate that egfl7 (VE-statin) promotes tumor cell evasion from the immune system by repressing endothelial cell activation, preventing immune cells from entering the tumor mass. In the present study, the expression levels of egfl7 and that of ICAM-1 as a marker of endothelium activation, were evaluated in peritumoral vessels of human breast cancer samples. Breast cancer samples (174 invasive and 30in situ) from 204 patients treated in 2005 were immunostained for CD31, ICAM-1 and stained for egfl7 usingin situhybridization. The expression levels of ICAM-1 and egfl7 were assessed in peritumoral areas using semi-quantitative scales. There was a strong and significant inverse correlation between the expression of ICAM-1 and that of egfl7 in CD31+blood vessels. When the ICAM-1 score increased, the egfl7 score reduced significantly (P=0.004), and vice-versa (Cuzick's test for trend across ordered groups). In order to determine which gene influenced the other gene between egfl7 and ICAM-1, the expression levels of either gene were modulated in endothelial cells. Egfl7 regulated ICAM-1 expression while ICAM-1 had no effects on egfl7 expression in the same conditions. Altogether, these results provide further results that egfl7 serves a regulatory role in endothelial cell activation in relation to immune infiltration and that it is a potential therapeutic target to consider for improving anticancer immunotherapies.
authors.affiliation: Senology Department, Oscar Lambret Center, Université de Lille, 59020 Lille, France; Institut Pasteur de Lille, Centre National de la Recherche Scientifique UMR8161, Université de Lille, 59000 Lille, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Pannier
authors.affiliation: Senology Department, Oscar Lambret Center, Université de Lille, 59020 Lille, France; Institut Pasteur de Lille, Centre National de la Recherche Scientifique UMR8161, Université de Lille, 59000 Lille, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Philippin-Lauridant
authors.affiliation: Senology Department, Oscar Lambret Center, Université de Lille, 59020 Lille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Baranzelli
authors.affiliation: Senology Department, Oscar Lambret Center, Université de Lille, 59020 Lille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Bertin
authors.affiliation: Senology Department, Oscar Lambret Center, Université de Lille, 59020 Lille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Bogart
authors.affiliation: Institut Pasteur de Lille, Centre National de la Recherche Scientifique UMR8161, Université de Lille, 59000 Lille, France.
authors.forename: Victor
authors.initials: V
authors.lastname: Delprat
authors.affiliation: Institut Pasteur de Lille, Centre National de la Recherche Scientifique UMR8161, Université de Lille, 59000 Lille, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Villain
authors.affiliation: Institut Pasteur de Lille, Centre National de la Recherche Scientifique UMR8161, Université de Lille, 59000 Lille, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Mattot
authors.affiliation: Senology Department, Oscar Lambret Center, Université de Lille, 59020 Lille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bonneterre
authors.affiliation: Institut Pasteur de Lille, Centre National de la Recherche Scientifique UMR8161, Université de Lille, 59000 Lille, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Soncin
keywords: blood vessels; breast cancer; endothelium activation; immunity