Trichosanthin increases Granzyme B penetration into tumor cells by upregulation of CI-MPR on the cell surface.
Trichosanthin increases Granzyme B penetration into tumor cells by upregulation of CI-MPR on the cell surface.
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DOI：
10.18632/oncotarget.15518
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发表时间：
2017-04-18
期刊：
影响因子：
--
通讯作者：
Sha O
中科院分区：
文献类型：
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作者：
Li C;Zeng M;Chi H;Shen J;Ng TB;Jin G;Lu D;Fan X;Xiong B;Xiao Z;Sha O
天花粉蛋白是一种植物毒素，属于核糖体失活蛋白家族。它具有多种生物学和药理学活性，包括抗肿瘤和免疫调节作用。在这项研究中，我们探索了潜在的药物应用中的癌症免疫治疗。我们发现，天花粉蛋白和阳离子非依赖性甘露糖-6-磷酸受体竞争性结合高尔基体定位的，γ-耳含和Arf结合蛋白。进而促进阳离子非依赖性甘露糖-6-磷酸受体从胞质溶胶转运至质膜，该受体是颗粒酶B的受体。肿瘤细胞表面该受体的上调增加了细胞对颗粒酶B的通透性，而后者是细胞毒性T淋巴细胞介导的肿瘤细胞凋亡的主要因素之一。这些结果表明，一个新的潜在的应用，并揭示了其抗肿瘤免疫治疗。
Trichosanthin is a plant toxin belonging to the family of ribosome-inactivating proteins. It has various biological and pharmacological activities, including anti-tumor and immunoregulatory effects. In this study, we explored the potential medicinal applications of trichosanthin in cancer immunotherapy. We found that trichosanthin and cation-independent mannose-6-phosphate receptor competitively bind to the Golgi-localized, γ-ear containing and Arf-binding proteins. It in turn promotes the translocation of cation-independent mannose-6-phosphate receptor from the cytosol to the plasma membrane, which is a receptor of Granzyme B. The upregulation of this receptor on the tumor cell surface increased the cell permeability to Granzyme B, and the latter is one of the major factors of cytotoxic T lymphocyte-mediated tumor cell apoptosis. These results suggest a novel potential application of trichosanthin and shed light on its anti-tumor immunotherapy.