Signaling mechanisms in infantile hemangioma.
Signaling mechanisms in infantile hemangioma.
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DOI：
10.1097/moh.0b013e32832a07ff
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发表时间：
2009-05
影响因子：
3.2
通讯作者：
Olsen BR
中科院分区：
文献类型：
--
作者：
Boye E;Olsen BR
婴儿血管瘤是一种常见的血管肿瘤，具有独特的生命周期：婴儿期快速生长，随后一段时间消退，导致完全消退。本文综述了近年来关于血管瘤形成的分子机制的研究，并结合以往的研究成果提出了新的发现和假说。这项新工作发现了血管内皮细胞中血管生长因子和细胞外基质调节的新信号通路，并为新的治疗策略提供了基础。在血管瘤来源的内皮细胞中，血管内皮生长因子受体/整合素复合体的缺陷会减少血管内皮生长因子诱骗受体的表达。因此，血管瘤内皮细胞表现出结构性的血管内皮生长因子信号。一些血管瘤患者中生长因子受体/整合素复合体成分的胚系突变，以及散发性血管瘤标本中磷酸酶的体细胞突变，增加了血管瘤形成涉及种系风险因子突变和体细胞突变的可能性，类似于最近的研究表明静脉畸形的情况。血管内皮细胞中负调控血管内皮生长因子信号的通路的改变是婴儿血管瘤形成和快速生长的原因。
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. 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. Germ-line 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. 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.