Blood：开发出治疗淋巴瘤的新型疗法

来自加利福利亚大学洛杉矶分校Jonsson综合癌症中心的研究者通过研究发现了一种实验性药物GCS-100移除淋巴瘤特定蛋白的分子机制，这种淋巴瘤特定蛋白可以抑制细胞对化疗产生反应。相关研究成果刊登在近日的国际杂志Blood上。

文章中，研究者希望将GCS-100结合化疗方法来开发出治疗弥散性B细胞淋巴瘤（DLBCL）的方法。弥散性B细胞淋巴瘤是常见的致死性的非霍奇金淋巴瘤，一种免疫系统癌症。

研究人员发现蛋白质半乳凝素3可以结合到淋巴瘤细胞表面的CD45酶上，这种蛋白质和酶的结合可以调节癌细胞对于化疗的敏感性，尤其是当其保护癌细胞免受化疗药物损伤的时候。

GCS-100分离自柑橘果胶，其通常在癌细胞外部工作来移除保护性的半乳凝素3，一旦半乳凝素3被移除，淋巴瘤细胞就会被化疗药物杀灭。尽管化疗药物可以有效杀灭肿瘤细胞，但是GCS-100的加入可以增加化疗药物杀灭癌细胞的效率。

研究者Linda表示，这种新型药物已经不再使用，我们希望临床试验中可以继续使用这种药物，我们的研究揭示，其可以有效帮助化疗方法来剔除淋巴瘤细胞。早期的GCS-100临床试验揭示了其并无任何副作用，而且其可以促进T细胞的发育，这就更能够帮助免疫系统战胜疾病。

与淋巴瘤相关的拓展阅读：

• JCO：【评论】治疗滤泡性淋巴瘤的“一线之争”
• J Infect Dis：银屑病发生皮肤T细胞淋巴瘤风险高
• Lancet Oncol：Crizotinib可用于治疗炎性肌纤维母细胞瘤和间变性大细胞淋巴瘤儿童患者
• JNCI：抑制肉碱乙酰基转移酶可预防Myc诱导的淋巴瘤生成
• NEJM：利妥昔单抗方案治疗纵隔B细胞淋巴瘤可避免放疗 更多信息请点击：有关淋巴瘤更多资讯

Galectin-3 binds to CD45 on diffuse large B cell lymphoma cells to regulate susceptibility to cell death

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma and an aggressive malignancy. Galectin-3 (gal-3), the only anti-apoptotic member of the galectin family, is overexpressed in DLBCL. While gal-3 can localize to intracellular sites, gal-3 is secreted by DLBCL cells and binds back to the cell surface in a carbohydrate-dependent manner. The major counterreceptor for gal-3 on DLBCL cells was identified as the transmembrane tyrosine phosphatase CD45. Removal of cell surface gal-3 from CD45 with the polyvalent glycan inhibitor GCS-100 rendered DLBCL cells susceptible to chemotherapeutic agents. Binding of gal-3 to CD45 modulated tyrosine phosphatase activity; removal of endogenous cell surface gal-3 from CD45 with GCS-100 increased phosphatase activity, while addition of exogenous gal-3 reduced phosphatase activity. Moreover, the increased susceptibility of DLBCL cells to chemotherapeutic agents after removal of gal-3 by GCS-100 required CD45 phosphatase activity. Gal-3 binding to a subset of highly glycosylated CD45 glycoforms was regulated by the C2GnT-1 glycosyltransferase, indicating that specific glycosylation of CD45 is important for regulation of gal-3-mediated signaling. These data identify a novel role for cell surface gal-3 and CD45 in DLBCL survival and suggest novel therapeutic targets to sensitize DLBCL cells to death.