title: Identification of IGPR-1 as a novel adhesion molecule involved in angiogenesis.
abstract: Angiogenesis-the growth of new blood vessels from preexisting vessels-is an important physiological process and is considered to play a key role in tumor growth and metastasis. We identified the immunoglobulin-containing and proline-rich receptor-1 (IGPR-1, also called TMIGD2) gene as a novel cell adhesion receptor that is expressed in various human organs and tissues, mainly in cells with epithelium and endothelium origins. IGPR-1 regulates cellular morphology, homophilic cell aggregation, and cell-cell interaction. IGPR-1 activity also modulates actin stress fiber formation and focal adhesion and reduces cell migration. Silencing of expression of IGPR-1 by small interfering RNA (siRNA) and by ectopic overexpression in endothelial cells showed that IGPR-1 regulates capillary tube formation in vitro, and B16F melanoma cells engineered to express IGPR-1 displayed extensive angiogenesis in the mouse Matrigel angiogenesis model. Moreover, IGPR-1, through its proline-rich cytoplasmic domain, associates with multiple Src homology 3 (SH3)-containing signaling proteins, including SH3 protein interacting with Nck (SPIN90/WISH), bullous pemphigoid antigen-1, and calcium channel β2. Silencing of expression of SPIN90/WISH by siRNA in endothelial cells showed that SPIN90/WISH is required for capillary tube formation. These features of IGPR-1 suggest that IGPR-1 is a novel receptor that plays an important role in cell-cell interaction, cell migration, and angiogenesis.
authors.affiliation: Departments of Pathology and Ophthalmology, School of Medicine, Boston University, Boston, MA 02118, USA. nrahimi@bu.edu
authors.forename: Nader
authors.initials: N
authors.lastname: Rahimi
authors.forename: Kobra
authors.initials: K
authors.lastname: Rezazadeh
authors.forename: John E
authors.initials: JE
authors.lastname: Mahoney
authors.forename: Edward
authors.initials: E
authors.lastname: Hartsough
authors.forename: Rosana D
authors.initials: RD
authors.lastname: Meyer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D018106:CD28 Antigens; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008546:Melanoma, Experimental / Q000098:blood supply / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; D015815:Cell Adhesion Molecules; D009124:Muscle Proteins; C486062:NCKIPSD protein, human; D011956:Receptors, Cell Surface; C585279:TMIGD2 protein, human