title: Identification of soluble CD146 as a regulator of trophoblast migration: potential role in placental vascular development.
abstract: Both vasculogenesis and angiogenesis occur during normal placental vascular development. Additionally, the placenta undergoes a process of vascular mimicry (pseudo-vasculogenesis) where the placental extravillous trophoblast (EVT) that invade the spiral arteries convert from an epithelial to an endothelial phenotype during normal pregnancy. As soluble CD146 (sCD146) constitutes a new physiological factor with angiogenic properties, we hypothesized that it could be involved in the regulation of placental vascular development by acting on EVT. Using placental villous explants, we demonstrated that sCD146 inhibits EVT outgrowth. Consistently, we showed that sCD146 inhibits the ability of EVT cells (HTR8/SVneo) to migrate, invade and form tubes in Matrigel, without affecting their proliferation or apoptosis. The involvement of sCD146 in human pregnancy was investigated by evaluation of sCD146 levels in 50 pregnant women. We observed physiological down-regulation of sCD146 throughout pregnancy. These results prompted us to investigate the effect of prolonged sCD146 administration in a rat model of pregnancy. Repeated systemic sCD146 injections after coupling caused a significant decrease of pregnancy rate and number of embryos. Histological studies performed on placenta evidenced a reduced migration of glycogen cells (analogous to EVT in rat) in sCD146-treated rats. We propose that in human, sCD146 could represent both an attractive biomarker of placental vascular development and a therapeutic target in pregnancy complications associated with pathological angiogenesis.
authors.affiliation: Inserm UMR-S 1076, Faculté de Pharmacie, Aix-Marseille University, 27 Bd Jean Moulin, 13385, Marseille Cedex 05, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Kaspi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Guillet
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Piercecchi-Marti
authors.forename: Nadia
authors.initials: N
authors.lastname: Alfaidy
authors.forename: Florence
authors.initials: F
authors.lastname: Bretelle
authors.forename: Alexandrine
authors.initials: A
authors.lastname: Bertaud-Foucault
authors.forename: Jimmy
authors.initials: J
authors.lastname: Stalin
authors.forename: Laka
authors.initials: L
authors.lastname: Rambeloson
authors.forename: Odile
authors.initials: O
authors.lastname: Lacroix
authors.forename: Marcel
authors.initials: M
authors.lastname: Blot-Chabaud
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bardin
mesh_terms: D000818:Animals; D051929:CD146 Antigen / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005298:Fertility / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D051381:Rats; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D051929:CD146 Antigen; C497902:MCAM protein, human