Department of Physiology and Pharmacology, Medical Sciences Building, Western University, London, ON, N6A 5C1, Canada,
J Cell Commun Signal. 2014 Mar;8(1):65-6. doi: 10.1007/s12079-013-0211-9. Epub 2013 Nov 6.
Melanoma is becoming increasingly common in recent years and has a very high mortality rate, owing largely to its highly metastatic nature. It tends to metastasize early in the course of the disease, and after metastasis is resistant to most current therapies. Preclinical data has indicated that heparin administered to patients as an antithrombotic treatment also has anti-metastatic properties. Heparin has been shown to interfere with the binding of the integrin Very Late Antigen 4 (VLA-4) to its ligand Vascular Cell Adhesion Molecule 1 (VCAM-1) and in a recent paper the laboratory of Bendas (Thrombosis and Haemostasis, Prepublished online) demonstrated that CCN1 binds to VLA-4 and interference in this binding by heparin results in reduced strength of the VLA-4/VCAM-1 binding. This indicates that CCN1 might represent a good target for reducing the metastasis, and thus mortality, of melanoma.
近年来,黑色素瘤的发病率越来越高,死亡率也非常高,这主要是由于其高度转移性的特性。它往往在疾病早期就发生转移,而且转移后对大多数当前的治疗方法都有耐药性。临床前数据表明,肝素作为一种抗血栓治疗药物,也具有抗转移特性。肝素已被证明可以干扰整合素非常迟抗原 4(VLA-4)与其配体血管细胞黏附分子 1(VCAM-1)的结合,Bendas 实验室在最近的一篇论文(血栓形成与止血,预印本在线)中证明了 CCN1 与 VLA-4 结合,肝素对这种结合的干扰导致 VLA-4/VCAM-1 结合强度降低。这表明 CCN1 可能是减少黑色素瘤转移和死亡率的一个很好的靶点。