lewis-x-antigen and Hemangioma

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.. 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.. 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.. 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.. 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.

Topics: Age of Onset; Cell Lineage; Child; Drug Resistance, Neoplasm; Embryo, Mammalian; Endothelial Cells; Female; Hemangioma; Hemangioma, Capillary; Humans; Infant, Newborn; Lewis X Antigen; Neoplasms, Vascular Tissue; Neoplastic Stem Cells; Neoplastic Syndromes, Hereditary; Placenta; Placentation; Pregnancy; Pregnancy Trimester, First; Propranolol; Stem Cell Niche

Little is known about the pathogenesis of infantile hemangiomas despite the fact that they are relatively common tumors. These benign neoplasms occur in as many as 1 in 10 births, and although rarely life threatening, hemangiomas can pose serious concerns to the cosmetic and psychosocial development of the afflicted child. Ulceration, scarring, and disfigurement are significant problems as are encroachment of the ear and eye, which can threaten hearing and vision. The precise mechanisms controlling the rapid growth observed in the first months of life and the spontaneous involution that follows throughout the course of years remain unknown. In this report we demonstrate the presence of large numbers of hematopoietic cells of the myeloid lineage in proliferating hemangiomas and propose a mechanism for the observed evolution of these lesions that is triggered by hypoxia and involves the participation of myeloid cells. We report the results of experiments using myeloid markers (CD83, CD32, CD14, CD15) that unexpectedly co-labeled hemangioma endothelial cells, providing new evidence that these cells are distinct from normal endothelium.

Topics: Antigens, CD; CD83 Antigen; Cell Hypoxia; Cell Proliferation; Endothelium, Vascular; Hemangioma; Hemangioma, Capillary; Humans; Immunoglobulins; Infant; Lewis X Antigen; Lipopolysaccharide Receptors; Membrane Glycoproteins; Myeloid Cells; Receptors, IgG