title: The embryo-placental CD15-positive "vasculogenic zones" as a source of propranolol-sensitive pediatric vascular tumors.
abstract: OBJECTIVE
  Propranolol-induced involution is a unique biological feature of some pediatric vascular tumors, for instance infantile hemangioma (IH), cerebral cavernoma or chorioangioma. Currently, the cellular origin of these distinct tumors is unclear. In this study, we tested the hypothesis that propranolol-responsive vascular tumors are derived from common vessel-forming CD15 + progenitor cells which occur in early gestation. The aim of this study was to identify the tumor-relevant CD15 + progenitors at the early stages of embryo-placental development.
  
  
  METHODS
  Human embryo-placental units of 4-8 weeks gestation and pediatric vascular tumors were tested for expression of the tumor-relevant markers CD15, CD31 and CD34.
  
  
  RESULTS
  Placental vessel-forming progenitors were characterized by immunostaining for CD15, CD31, and CD34. In embryonic tissue, a discontinuous CD15+/CD31+/CD34 + progenitors was detected in immature vessels of the skin, neural tube, spinal and cerebral meninges. Similarly, vessels in IH and chorioangioma exhibited a co-expression of CD15, CD31, and CD34. In contrast, the majority of embryonic vessels presented a CD31+/CD34+, but CD15-negative immunophenotypic pattern.
  
  
  CONCLUSIONS
  Our results suggest the existence of a CD15+ "vasculogenic zones" in the embryo-placental unit as well as in IH and chorioangioma. A site-specific correlation between normal embryo-placental and tumoral vessel-forming CD15 + progenitors was demonstrated.
  
  
  CONCLUSIONS
  Hence, site- and stage-specific CD15 + progenitors of vascular wall could be considered as propronalol-sensitive targets and source of pre- and postnatal vascular tumors. We propose, that the CD15+ "vasculogenic zones" are a site-specific reserve of multi-lineage progenitors that could be recruited in pre- and postnatal emergency situations.
authors.affiliation: Institute of Pathology, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany. Electronic address: larissa.seidmann@mail.ru.
authors.forename: L
authors.initials: L
authors.lastname: Seidmann
authors.affiliation: Institute of Pathology, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Anspach
authors.affiliation: Institute of Pathology, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Roth
mesh_terms: D017668:Age of Onset; D019070:Cell Lineage; D002648:Child; D019008:Drug Resistance, Neoplasm; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006391:Hemangioma / Q000378:metabolism / Q000473:pathology; D018324:Hemangioma, Capillary / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D016256:Lewis X Antigen / Q000378:metabolism*; D009383:Neoplasms, Vascular Tissue / Q000453:epidemiology / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009386:Neoplastic Syndromes, Hereditary / Q000378:metabolism / Q000473:pathology; D010920:Placenta / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011433:Propranolol; D055153:Stem Cell Niche
chemical_list: D016256:Lewis X Antigen; D011433:Propranolol
keywords: CD15; Cerebral cavernoma; Infantile hemangioma; Placenta; Vasculogenic zone; propranolol