Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey, United States of America.
PLoS One. 2012;7(7):e41845. doi: 10.1371/journal.pone.0041845. Epub 2012 Jul 23.
Cancer is a leading cause of death of men and women worldwide. Tumor cell motility contributes to metastatic invasion that causes the vast majority of cancer deaths. Extracellular receptors modified by α2,3-sialic acids that promote this motility can serve as ideal chemotherapeutic targets. For example, the extracellular domain of the mucin receptor podoplanin (PDPN) is highly O-glycosylated with α2,3-sialic acid linked to galactose. PDPN is activated by endogenous ligands to induce tumor cell motility and metastasis. Dietary lectins that target proteins containing α2,3-sialic acid inhibit tumor cell growth. However, anti-cancer lectins that have been examined thus far target receptors that have not been identified. We report here that a lectin from the seeds of Maackia amurensis (MASL) with affinity for O-linked carbohydrate chains containing sialic acid targets PDPN to inhibit transformed cell growth and motility at nanomolar concentrations. Interestingly, the biological activity of this lectin survives gastrointestinal proteolysis and enters the cardiovascular system to inhibit melanoma cell growth, migration, and tumorigenesis. These studies demonstrate how lectins may be used to help develop dietary agents that target specific receptors to combat malignant cell growth.
癌症是全球男性和女性的主要死亡原因之一。肿瘤细胞的运动能力有助于转移性浸润，这是导致绝大多数癌症死亡的主要原因。经过α2,3-唾液酸修饰的细胞外受体促进了这种运动能力，可作为理想的化疗靶点。例如，黏蛋白受体 podoplanin（PDPN）的细胞外结构域高度 O-糖基化，α2,3-唾液酸与半乳糖相连。PDPN 通过内源性配体激活诱导肿瘤细胞运动和转移。靶向含有α2,3-唾液酸的蛋白质的膳食凝集素可抑制肿瘤细胞生长。然而，迄今为止检查过的抗癌凝集素针对的是尚未确定的受体。我们在这里报告，来自 Maackia amurensis（MASL）种子的凝集素（MASL）对含有唾液酸的 O-连接碳水化合物链具有亲和力，可靶向 PDPN 抑制转化细胞的生长和运动，其浓度低至纳摩尔。有趣的是，这种凝集素的生物学活性在胃肠道蛋白水解作用下得以存活，并进入心血管系统，抑制黑色素瘤细胞的生长、迁移和肿瘤发生。这些研究表明，凝集素如何可用于帮助开发针对特定受体的饮食制剂，以对抗恶性细胞生长。
