title: A peptide inhibitor of synuclein-γ reduces neovascularization of human endometriotic lesions.
abstract: Endometriosis is a chronic painful gynecological condition characterized by adherence and growth of endometrium outside of the uterine cavity. Neovascularization is essential to the developing endometriosis lesion to support its growth. Synuclein-γ (SNCG), a protein implicated in cellular proliferation, is associated with a broad range of malignancies as well as endometriosis. We hypothesized that SNCG plays an important role in the neovascularization and growth of endometriosis and blocking of SNCG will interfere with survival of endometriotic lesions in a mouse model. We developed SP012, a novel 12 amino acid peptide inhibitor of SNCG. SP012 inhibited three-dimensional endothelial cell tube formation in a dose-dependent manner. Using intravital microscopy, SP012 was shown to be successfully delivered to human endometriotic lesions in a xenograft mouse model in vivo. Alymphoid (BALB/c-Rag2-/-Il2rγ-/- lacking T, B and NK cells) mice were surgically induced with human endometriotic lesions and treated with SP012 or phosphate-buffered saline control. SP012 treated endometriotic lesions had decreased growth, development and vascularization at the time of necroscopy. Endometriotic lesions treated with SP012 also had fewer isolectin (+) microvessels. These results, using a mouse model, indicate that SNCG plays a role in the neovascularization and subsequent growth of human endometriotic lesions. Targeting SNCG function using peptide inhibitor might provide a potential therapeutic option for the treatment of endometriosis in the future.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada, K7L 3N6.
authors.forename: Andrew Kenneth
authors.initials: AK
authors.lastname: Edwards
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada, K7L 3N6.
authors.forename: Sharanya
authors.initials: S
authors.lastname: Ramesh
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada, K7L 3N6 tayadec@queensu.ca singhv@queensu.ca.
authors.forename: Vinay
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada, K7L 3N6 tayadec@queensu.ca singhv@queensu.ca.
authors.forename: Chandrakant
authors.initials: C
authors.lastname: Tayade
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy / Q000473:pathology*; D004717:Endometrium / Q000098:blood supply* / Q000473:pathology / Q000637:transplantation; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010455:Peptides / Q000494:pharmacology; D014183:Transplantation, Heterologous; D051845:gamma-Synuclein / Q000037:antagonists & inhibitors*
chemical_list: D037102:Lectins; D009363:Neoplasm Proteins; D010455:Peptides; C104249:SNCG protein, human; D051845:gamma-Synuclein
keywords: angiogenesis; endometriosis; endothelial cells; mouse model; synuclein-gamma