Mach Robert Henry, Wheeler Kenneth Theodore
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cent Nerv Syst Agents Med Chem. 2009 Sep;9(3):230-45. doi: 10.2174/1871524910909030230.
The sigma-2 (sigma(2)) receptor is proving to be an important protein in the field of cancer biology. The observations that sigma(2) receptors have a 10-fold higher density in proliferating tumor cells than in quiescent tumor cells, and that sigma(2) receptor agonists are capable of killing tumor cells via apoptotic and non-apoptotic mechanisms, indicate that this receptor is an important molecular target for the development of radiotracers for imaging tumors using techniques such as Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) and for the development of cancer chemotherapeutic agents. In spite of recent promising results towards achieving these goals, research in this field has been hampered by the fact that the molecular identity of the protein sequence of the sigma(2) receptor is currently not known. Consequently, most of what is known about this protein has been obtained using either radiolabeled or fluorescent probes for this receptor, or biochemical analysis of the effect of sigma(2) selective ligands on cells growing under tissue culture conditions. This article provides a review of the development and use of sigma(2) receptor ligands, and how these ligands have been used with a variety of in vitro and in vivo models to gain a greater understanding of the role this receptor plays in cancer.
σ-2（σ(2)）受体在癌症生物学领域正被证明是一种重要的蛋白质。σ(2)受体在增殖的肿瘤细胞中的密度比静止的肿瘤细胞高10倍，且σ(2)受体激动剂能够通过凋亡和非凋亡机制杀死肿瘤细胞，这些观察结果表明，该受体是开发用于正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）等技术成像肿瘤的放射性示踪剂以及癌症化疗药物的重要分子靶点。尽管最近在实现这些目标方面取得了令人鼓舞的结果，但该领域的研究受到了σ(2)受体蛋白质序列的分子身份目前尚不清楚这一事实的阻碍。因此，关于这种蛋白质的大部分已知信息是通过使用针对该受体的放射性标记或荧光探针，或对σ(2)选择性配体对在组织培养条件下生长的细胞的影响进行生化分析获得的。本文综述了σ(2)受体配体的开发和应用，以及这些配体如何与各种体外和体内模型一起使用，以更深入地了解该受体在癌症中所起的作用。
