title: Glucose transporter 1-positive endothelial cells in infantile hemangioma exhibit features of facultative stem cells.
abstract: Endothelial glucose transporter 1 (GLUT1) is a definitive and diagnostic marker for infantile hemangioma (IH), a vascular tumor of infancy. To date, GLUT1-positive endothelial cells in IH have not been quantified nor directly isolated and studied. We isolated GLUT1-positive and GLUT1-negative endothelial cells from IH specimens and characterized their proliferation, differentiation, and response to propranolol, a first-line therapy for IH, and to rapamycin, an mTOR pathway inhibitor used to treat an increasingly wide array of proliferative disorders. Although freshly isolated GLUT1-positive cells, selected using anti-GLUT1 magnetic beads, expressed endothelial markers CD31, VE-Cadherin, and vascular endothelial growth factor receptor 2, they converted to a mesenchymal phenotype after 3 weeks in culture. In contrast, GLUT1-negative endothelial cells exhibited a stable endothelial phenotype in vitro. GLUT1-selected cells were clonogenic when plated as single cells and could be induced to redifferentiate into endothelial cells, or into pericytes/smooth muscle cells or into adipocytes, indicating a stem cell-like phenotype. These data demonstrate that, although they appear and function in the tumor as bona fide endothelial cells, the GLUT1-positive endothelial cells display properties of facultative stem cells. Pretreatment with rapamycin for 4 days significantly slowed proliferation of GLUT1-selected cells, whereas propranolol pretreatment had no effect. These results reveal for the first time the facultative nature of GLUT1-positive endothelial cells in IH.
authors.affiliation: Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA; Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Hironao
authors.initials: H
authors.lastname: Nakayama
authors.forename: Michael
authors.initials: M
authors.lastname: Klagsbrun
authors.forename: John B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006391:Hemangioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011433:Propranolol / Q000494:pharmacology; D020123:Sirolimus / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D011433:Propranolol; D020123:Sirolimus
keywords: Endothelial cells; Facultative stem cells; Glucose transporter 1; Infantile hemangioma