title: Identifying potential regulators of infantile hemangioma progression through large-scale expression analysis: a possible role for the immune system and indoleamine 2,3 dioxygenase (IDO) during involution.
abstract: Hemangiomas are benign endothelial tumors. Often referred to as hemangiomas of infancy (HOI), these tumors are the most common tumor of infancy. Most of these lesions proliferate rapidly in the first months of life, and subsequently slowly involute during early childhood without significant complications. However, they often develop on the head or neck, and may pose a significant cosmetic concern for families. In addition, a fraction of these tumors can grow explosively and ulcerate, bleed, or obstruct vision or airway structures. Current treatments for these tumors are associated with significant side effects, and our knowledge of the biology of hemangiomas is limited. The natural evolution of these lesions creates a unique opportunity to study the changes in gene expression that occur as the endothelium of these tumors proliferates and then subsequently regresses. Such information may also increase our understanding of the basic principals of angiogenesis in normal and abnormal tissue. We have performed large-scale genomic analysis of hemangioma gene expression using DNA microarrays. We recently identified insulin-like growth factor 2 as a potentially important regulator of hemangioma growth using this approach. However, little is known about the mechanisms involved in hemangioma involution. Here we explore the idea that hemangioma involution might be an immune-mediated process and present data to support this concept. We also demonstrate that proliferating hemangiomas express indoleamine 2,3 dioxygenase (IDO) and discuss a possible mechanism that accounts for the often slow regression of these lesions.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Ritter
authors.forename: Stacey K
authors.initials: SK
authors.lastname: Moreno
authors.forename: Michael I
authors.initials: MI
authors.lastname: Dorrell
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rubens
authors.forename: Joshua
authors.initials: J
authors.lastname: Ney
authors.forename: David Fallon
authors.initials: DF
authors.lastname: Friedlander
authors.forename: James
authors.initials: J
authors.lastname: Bergman
authors.forename: Bari B
authors.initials: BB
authors.lastname: Cunningham
authors.forename: Lawrence
authors.initials: L
authors.lastname: Eichenfield
authors.forename: John
authors.initials: J
authors.lastname: Reinisch
authors.forename: Steven
authors.initials: S
authors.lastname: Cohen
authors.forename: Thomas
authors.initials: T
authors.lastname: Veccione
authors.forename: Ralph
authors.initials: R
authors.lastname: Holmes
authors.forename: Sheila Fallon
authors.initials: SF
authors.lastname: Friedlander
authors.forename: Martin
authors.initials: M
authors.lastname: Friedlander
mesh_terms: D017252:CD3 Complex / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D049308:Dioxygenases; D018450:Disease Progression; D006391:Hemangioma / Q000276:immunology* / Q000473:pathology*; D018324:Hemangioma, Capillary; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014366:Tryptophan Oxygenase / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D017252:CD3 Complex; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007335:Insulin-Like Growth Factor II; D049308:Dioxygenases; D014366:Tryptophan Oxygenase