Signaling mechanisms in infantile hemangioma.
OBJECTIVE
Infantile hemangioma is a common vascular tumor with a unique lifecycle: rapid growth in infancy, followed by a period of involution, leading to complete regression. This review summarizes recent studies of molecular mechanisms of hemangioma formation and places new findings and hypotheses in the context of past accomplishments.


RESULTS
The new work identifies a novel signaling pathway for vascular growth factor and extracellular matrix regulation in vascular endothelial cells and provides a basis for novel therapeutic strategies. In hemangioma-derived endothelial cells, defects in a vascular endothelial growth factor receptor/integrin complex reduce the expression of a vascular endothelial growth factor decoy receptor. As a consequence, hemangioma endothelial cells exhibit constitutive vascular endothelial growth factor signaling. Germline mutations in components of the growth factor receptor/integrin complex in some hemangioma patients, and somatic mutations in a phosphatase in sporadic hemangioma specimens, raise the possibility that hemangioma formation involves a combination of germline risk factor mutations and somatic mutations, similar to what recent studies have shown is the case for venous malformations.


CONCLUSIONS
Alterations in pathways that negatively control vascular endothelial growth factor signaling in vascular endothelial cells are responsible for the formation and rapid growth of infantile hemangiomas.
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
Eileen
E
Boye
Bjorn R
BR
Olsen
D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006391:Hemangioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019012:Integrin beta1 / Q000378:metabolism; D008840:Microfilament Proteins; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D050778:NFATC Transcription Factors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D019043:Vascular Neoplasms / Q000378:metabolism* / Q000473:pathology
C473287:ANTXR1 protein, human; D019012:Integrin beta1; D008840:Microfilament Proteins; D050778:NFATC Transcription Factors; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2