Boye Eileen, Olsen Bjorn R
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
Curr Opin Hematol. 2009 May;16(3):202-8. doi: 10.1097/MOH.0b013e32832a07ff.
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. 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.
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.
婴儿血管瘤是一种常见的血管肿瘤，具有独特的生命周期：在婴儿期快速生长，随后进入消退期，最终完全消退。本综述总结了近期关于血管瘤形成分子机制的研究，并将新发现和假设置于以往研究成果的背景下进行探讨。
新的研究确定了血管内皮细胞中血管生长因子和细胞外基质调节的一种新信号通路，为新的治疗策略提供了依据。在血管瘤来源的内皮细胞中，血管内皮生长因子受体/整合素复合物的缺陷会降低血管内皮生长因子诱饵受体的表达。因此，血管瘤内皮细胞表现出组成性血管内皮生长因子信号传导。一些血管瘤患者生长因子受体/整合素复合物成分的种系突变，以及散发性血管瘤标本中一种磷酸酶的体细胞突变，增加了血管瘤形成涉及种系危险因素突变和体细胞突变组合的可能性，这与近期关于静脉畸形的研究所显示的情况类似。
血管内皮细胞中负性调控血管内皮生长因子信号传导的通路改变是婴儿血管瘤形成和快速生长的原因。
