Wu June K, Kitajewski Jan K
Departments of Surgery, Columbia University College of Physicians and Surgeons, New York, New York, USA.
J Craniofac Surg. 2009 Mar;20 Suppl 1(0 1):698-702. doi: 10.1097/SCS.0b013e318193d898.
Hemangiomas are the most common benign tumor of infancy, yet its pathogenesis and the mechanisms governing proliferation and involution are not well understood. It is believed that hemangiomas arise out of clonal, abnormal hemangioma endothelial cells (HemECs). The underlying anomaly of the HemEC is not known, although studies have shown that vascular endothelial growth factor (VEGF) and VEGF signaling may influence HemECs. Moreover, there are numerous subtypes of hemangiomas, with differences in natural history, potential for morbidity, and prognosis, and little is known how this relates to HemEC. The Notch signaling pathway is a highly conserved pathway across species from worms to mammals. Notch signaling has been shown to play a role during embryogenesis in directing vascular patterning and development and arterial and venous cell fate determination. Postnatally, it has been implicated in tumor angiogenesis in multiple malignancies. Notch signaling triggers tumor angiogenesis at least in part to stimulation by VEGF, thus establishing that there is a cross talk between the VEGF and Notch pathways. Given the presence of VEGF and its receptors in hemangiomas and known VEGF-Notch cross talk in tumor angiogenesis, the authors hypothesize that Notch signaling may contribute to hemangioma proliferation and involution. Preliminary studies of resected hemangioma specimens by reverse transcription polymerase chain reaction (RT-PCR) show that all 4 Notch receptors and 2 Notch ligands, Jagged1 and Delta-like ligand 4, are expressed by hemangiomas. These findings support a role for Notch in hemangiomas, meriting further analysis of the functional relevance of Notch signaling in hemangiomas.
血管瘤是婴儿期最常见的良性肿瘤，但其发病机制以及控制增殖和消退的机制尚未完全明确。人们认为血管瘤起源于克隆性、异常的血管瘤内皮细胞（HemECs）。尽管研究表明血管内皮生长因子（VEGF）及其信号传导可能影响HemECs，但HemECs潜在的异常情况尚不清楚。此外，血管瘤有众多亚型，其自然病史、发病可能性和预后存在差异，而对于这些与HemECs的关系知之甚少。Notch信号通路是从蠕虫到哺乳动物的跨物种高度保守的信号通路。研究表明，Notch信号在胚胎发育过程中对指导血管模式形成、发育以及动脉和静脉细胞命运的决定发挥作用。出生后，它与多种恶性肿瘤的肿瘤血管生成有关。Notch信号至少部分通过VEGF刺激触发肿瘤血管生成，从而证实VEGF和Notch信号通路之间存在相互作用。鉴于血管瘤中存在VEGF及其受体以及肿瘤血管生成中已知的VEGF-Notch相互作用，作者推测Notch信号可能与血管瘤的增殖和消退有关。通过逆转录聚合酶链反应（RT-PCR）对切除的血管瘤标本进行的初步研究表明，所有4种Notch受体以及2种Notch配体Jagged1和Delta样配体4均在血管瘤中表达。这些发现支持Notch在血管瘤中发挥作用，值得进一步分析Notch信号在血管瘤中的功能相关性。
