Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis
Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis
复制标题
DOI：
10.1073/pnas.1202653110
复制
发表时间：
2013-03-26
影响因子：
11.1
通讯作者：
Ahmed, Hafiz
中科院分区：
文献类型：
--
作者：
Guha, Prasun;Kaptan, Engin;Ahmed, Hafiz
肿瘤转移和免疫抑制是肿瘤治疗中的关键问题。在这里，我们发现β -半乳糖苷结合凝集素[galectin-3 (gal3)]识别存在于大多数癌细胞表面的Thomsen-Friedenreich双糖（TFD, Gal β 1,3 galnac），参与促进前列腺癌细胞的血管生成、肿瘤内皮细胞粘附和转移，以及通过杀死活化的T细胞逃避免疫监视。为了阻断gal3介导的相互作用，我们从鳕鱼中纯化了一种糖肽（指定为TFD100），该糖肽以小摩尔亲和力结合gal3。TFD100在纳摩尔水平上阻断gal3介导的血管生成、肿瘤内皮细胞相互作用和前列腺癌细胞转移。此外，在纳米摩尔浓度的TFD100下，重组gal3或前列腺癌患者血清相关gal3诱导的活化T细胞凋亡均被抑制。由于gal3-TFD相互作用是大多数上皮性癌症转移的关键因素，这种高亲和力的TFD100应该是一种有前途的抗转移药物，可用于治疗包括前列腺癌在内的各种癌症。
Cancer metastasis and immune suppression are critical issues in cancer therapy. Here, we show that a beta-galactoside-binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Gal beta 1,3GalNAc) present on the surface of most cancer cells is involved in promoting angiogenesis, tumor-endothelial cell adhesion, and metastasis of prostate cancer cells, as well as evading immune surveillance through killing of activated T cells. To block gal3-mediated interactions, we purified a glycopeptide from cod (designated TFD100) that binds gal3 with picomolar affinity. TFD100 blocks gal3-mediated angiogenesis, tumor-endothelial cell interactions, and metastasis of prostate cancer cells in mice at nanomolar levels. Moreover, apoptosis of activated T cells induced by either recombinant gal3 or prostate cancer patient serum-associated gal3 was inhibited at nanomolar concentration of TFD100. Because the gal3-TFD interaction is a key factor driving metastasis in most epithelial cancers, this high-affinity TFD100 should be a promising anti-metastatic agent for the treatment of various cancers, including prostate adenocarcinoma.