Muñoz Miguel, Coveñas Rafael
Research Laboratory on Neuropeptides, Hospital Infantil Universitario Virgen del Rocío, Sevilla 41013, Spain.
Discov Med. 2010 Oct;10(53):305-13.
Substance P (SP) has a widespread distribution in the whole body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates biological functions related to cancer: tumor cell proliferation (favoring tumor growth), angiogenesis, and migration of the tumor cells for invasion and metastasis. SP also exerts an antiapoptotic effect. The peptide is secreted from primary tumors and from peripheral nerves, and reaches the whole body through the blood stream. NK-1 receptors are overexpressed in tumors (cancer cells express more NK-1 receptors than normal cells). By contrast, after binding to NK-1 receptors, the NK-1 receptor antagonists specifically inhibit tumor cell proliferation (tumor cells die by apoptosis), angiogenesis and the migration of the tumor cells. Thus, 1) the SP/NK-1 receptor system plays an important role in the development of cancer, angiogenesis, and metastasis; 2) a common mechanism for cancer cell proliferation mediated by the SP/NK-1 receptor system occurs; 3) NK-1 receptor antagonists act as a broad-spectrum antitumoral agent; 4) the NK-1 receptor could be a new promising target in the treatment of cancer; 5) NK-1 receptor antagonists could improve cancer treatment--the development of antagonist molecules of the NK-1 receptor represents an important opportunity for exploiting these molecules as novel therapeutic agents.
P物质(SP)在全身广泛分布。与神经激肽-1(NK-1)受体结合后,SP调节与癌症相关的生物学功能:肿瘤细胞增殖(促进肿瘤生长)、血管生成以及肿瘤细胞的侵袭和转移迁移。SP还发挥抗凋亡作用。该肽由原发性肿瘤和外周神经分泌,并通过血流到达全身。NK-1受体在肿瘤中过度表达(癌细胞比正常细胞表达更多的NK-1受体)。相比之下,与NK-1受体结合后,NK-1受体拮抗剂可特异性抑制肿瘤细胞增殖(肿瘤细胞通过凋亡死亡)、血管生成和肿瘤细胞迁移。因此,1)SP/NK-1受体系统在癌症的发生、血管生成和转移中起重要作用;2)SP/NK-1受体系统介导的癌细胞增殖存在共同机制;3)NK-1受体拮抗剂作为一种广谱抗肿瘤药物;4)NK-1受体可能是癌症治疗中一个有前景的新靶点;5)NK-1受体拮抗剂可改善癌症治疗——开发NK-1受体拮抗剂分子代表了将这些分子用作新型治疗药物的重要机会。