Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration.
Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration.
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DOI：
10.1371/journal.pone.0041845
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Goldberg GS
中科院分区：
文献类型：
--
作者：
Ochoa-Alvarez JA;Krishnan H;Shen Y;Acharya NK;Han M;McNulty DE;Hasegawa H;Hyodo T;Senga T;Geng JG;Kosciuk M;Shin SS;Goydos JS;Temiakov D;Nagele RG;Goldberg GS
癌症是全世界男性和女性死亡的主要原因。肿瘤细胞运动性有助于转移性侵袭，导致绝大多数癌症死亡。由α 2，3-唾液酸修饰的细胞外受体可以促进这种运动，可以作为理想的化疗靶点。例如，粘蛋白受体podoplanin（PDPN）的细胞外结构域被与半乳糖连接的α 2，3-唾液酸高度O-糖基化。PDPN被内源性配体激活以诱导肿瘤细胞运动和转移。靶向含α 2，3-唾液酸蛋白质的膳食凝集素抑制肿瘤细胞生长。然而，迄今为止已经检查的抗癌凝集素靶向尚未鉴定的受体。我们在这里报告说，从种子的怀槐（MASL）与O-连接的糖链含有唾液酸的目标PDPN抑制转化细胞的生长和运动在纳摩尔浓度的亲和力凝集素。有趣的是，这种凝集素的生物活性在胃肠道蛋白水解中存活，并进入心血管系统以抑制黑色素瘤细胞生长、迁移和肿瘤发生。这些研究表明，凝集素可用于帮助开发针对特定受体的膳食制剂，以对抗恶性细胞生长。
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.
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DOI：
10.1042/bj20071216
发表时间：
2008-04-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Christou CM;Pearce AC;Watson AA;Mistry AR;Pollitt AY;Fenton-May AE;Johnson LA;Jackson DG;Watson SP;O'Callaghan CA
通讯作者：
O'Callaghan CA
影响因子：
4.4
作者：
Estler M;Boskovic G;Denvir J;Miles S;Primerano DA;Niles RM
通讯作者：
Niles RM
DOI：
10.1002/gcc.20808
发表时间：
2010-11
期刊：
Genes, chromosomes & cancer
影响因子：
--
作者：
Cortez MA;Nicoloso MS;Shimizu M;Rossi S;Gopisetty G;Molina JR;Carlotti C Jr;Tirapelli D;Neder L;Brassesco MS;Scrideli CA;Tone LG;Georgescu MM;Zhang W;Puduvalli V;Calin GA
通讯作者：
Calin GA
影响因子：
4.2
作者：
Cui, Hongxia;Lin, Yu;Liu, Jicheng
通讯作者：
Liu, Jicheng
影响因子：
11.2
作者：
Hoshino, Ayuko;Ishii, Genichiro;Ochiai, Atsushi
通讯作者：
Ochiai, Atsushi