title: Mechanisms of trophoblast migration, endometrial angiogenesis in preeclampsia: The role of decorin.
abstract: The objective of the present review is to synthesize the information on the cellular and molecular players responsible for maintaining a homeostatic balance between a naturally invasive human placenta and the maternal uterus in pregnancy; to review the roles of decorin (DCN) as a molecular player in this homeostasis; to list the common maladies associated with a break-down in this homeostasis, resulting from a hypo-invasive or hyper-invasive placenta, and their underlying mechanisms. We show that both the fetal components of the placenta, represented primarily by the extravillous trophoblast, and the maternal component represented primarily by the decidual tissue and the endometrial arterioles, participate actively in this balance. We discuss the process of uterine angiogenesis in the context of uterine arterial changes during normal pregnancy and preeclampsia. We compare and contrast trophoblast growth and invasion with the processes involved in tumorigenesis with special emphasis on the roles of DCN and raise important questions that remain to be addressed. Decorin (DCN) is a small leucine-rich proteoglycan produced by stromal cells, including dermal fibroblasts, chondrocytes, chorionic villus mesenchymal cells and decidual cells of the pregnant endometrium. It contains a 40 kDa protein core having 10 leucine-rich repeats covalently linked with a glycosaminoglycan chain. Biological functions of DCN include: collagen assembly, myogenesis, tissue repair and regulation of cell adhesion and migration by binding to ECM molecules or antagonising multiple tyrosine kinase receptors (TKR) including EGFR, IGF-IR, HGFR and VEGFR-2. DCN restrains angiogenesis by binding to thrombospondin-1, TGFβ, VEGFR-2 and possibly IGF-IR. DCN can halt tumor growth by antagonising oncogenic TKRs and restraining angiogenesis. DCN actions at the fetal-maternal interface include restraint of trophoblast migration, invasion and uterine angiogenesis. We demonstrate that DCN overexpression in the decidua is associated with preeclampsia (PE); this may have a causal role in PE by compromising endovascular differentiation of the trophoblast and uterine angiogenesis, resulting in poor arterial remodeling. Elevated DCN level in the maternal blood is suggested as a potential biomarker in PE.
authors.affiliation: a Department of Anatomy and Cell Biology , Schulich School of Medicine and Dentistry, the University of Western Ontario , London , Ontario , Canada.|b Department of Oncology , Schulich School of Medicine and Dentistry, the University of Western Ontario , London , Ontario , Canada.|c Chidren's Health Research Institute, Schulich School of Medicine and Dentistry, the University of Western Ontario , London , Ontario , Canada.
authors.forename: Peeyush K
authors.initials: PK
authors.lastname: Lala
authors.affiliation: a Department of Anatomy and Cell Biology , Schulich School of Medicine and Dentistry, the University of Western Ontario , London , Ontario , Canada.
authors.forename: Pinki
authors.initials: P
authors.lastname: Nandi
mesh_terms: D000818:Animals; D002465:Cell Movement; D058575:Decorin / Q000378:metabolism*; D004717:Endometrium / Q000098:blood supply* / Q000473:pathology; D005260:Female; D006801:Humans; D018919:Neovascularization, Physiologic; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology*; D011247:Pregnancy; D014327:Trophoblasts / Q000473:pathology*
chemical_list: D058575:Decorin
keywords: adhesion; angiogenesis; decidua; decorin; extravillous trophoblast; invasion; leucine rich proteoglycan; migration; placenta; preeclampsia; trophoblast; tumor growth and metastasis; tyrosine kinase receptors