title: Elevated IGF2 prevents leptin induction and terminal adipocyte differentiation in hemangioma stem cells.
abstract: Infantile hemangioma is a benign vascular tumor that exhibits a unique yet predictable lifecycle of rapid proliferation followed by spontaneous regression. Recent studies have identified that insulin-like growth factor-2 (IGF2), a fetal mitogen, is highly expressed during the proliferative phase of hemangioma growth. Since hemangiomas arise from CD133+ stem cells, high levels of IGF2 may regulate the activity of the stem cells and therefore, hemangioma growth. The aim of this study was to understand the functional significance of elevated IGF2 in hemangiomas. We show that IGF2 localizes to the CD133+ cells in hemangioma specimens. We, therefore, hypothesized that IGF2 may be regulating the plasticity of hemangioma stem cells. To test our hypothesis, we used CD133-selected cells from hemangiomas to knockdown the expression of IGF2. We found that IGF2 is a mitogen for hemangioma stem cells and prevents leptin induction and full terminal differentiation of hemangioma stem cells into adipocytes. We also show that IGF2 does not alter the initial commitment phase. These findings implicate an important role of IGF2 in expanding hemangioma stem cells and preventing terminal adipocyte differentiation.
authors.affiliation: Department of Pathology, University of Western Ontario, London ON, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kleiman
authors.forename: Emily C
authors.initials: EC
authors.lastname: Keats
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Chan
authors.forename: Zia A
authors.initials: ZA
authors.lastname: Khan
mesh_terms: D000071916:AC133 Antigen; D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis; D015703:Antigens, CD / Q000032:analysis; D002454:Cell Differentiation; D049109:Cell Proliferation; D006023:Glycoproteins / Q000032:analysis; D006391:Hemangioma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D008934:Mitogens; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000502:physiology*; D010455:Peptides / Q000032:analysis; D034622:RNA Interference; D034741:RNA, Small Interfering; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C035170:IGF2 protein, human; D020738:Leptin; D008934:Mitogens; C000606023:PROM1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering; D007335:Insulin-Like Growth Factor II