Institute of Molecular Biology, Medical College, Three Gorges University, 8 Daxue Road, Yichang, Hubei 443002, China.
Cell Mol Immunol. 2009 Dec;6(6):469-75. doi: 10.1038/cmi.2009.59.
In the process of cell apoptosis induced by specific reagents, calreticulin (CRT) in endoplasmic reticulum is transferred and coated onto the cell membrane. As a sort of specific ligand, the CRT on the surface of apoptotic cells could mediate recognition and clearance of apoptotic cells by phagocytes. In this research we discovered that mitoxantrone could induce apoptosis of mouse melonoma B16-F1 tumor cells, accompanied by the membrane translocation and coating of CRT. When mitoxantrone-treated B16-F1 cells were used as antigen to inoculate mice, the mice acquired an ability to suppress proliferation of homologous tumor cells. Splenocytes from these mice showed an increased cytolytic effect on homologous B16-F1 cells but no such effect on non-homologous H22 tumor cells. All these results suggested that mitoxantrone-treated apoptotic B16-F1 cells could be used as a sort of cell vaccine to initiate effective anti-tumor immunoresponse in mice.
在特定试剂诱导的细胞凋亡过程中,内质网中的钙网蛋白(CRT)会转移并覆盖在细胞膜上。作为一种特异性配体,凋亡细胞表面的 CRT 可以介导吞噬细胞对凋亡细胞的识别和清除。在这项研究中我们发现米托蒽醌能够诱导小鼠黑色素瘤 B16-F1 肿瘤细胞发生凋亡,伴随着 CRT 的膜转位和覆盖。当用米托蒽醌处理的 B16-F1 细胞作为抗原接种小鼠时,小鼠获得了抑制同源肿瘤细胞增殖的能力。来自这些小鼠的脾细胞对同源 B16-F1 细胞表现出增强的细胞毒性作用,但对非同源 H22 肿瘤细胞没有这种作用。所有这些结果表明,米托蒽醌处理的凋亡 B16-F1 细胞可用作一种细胞疫苗,在小鼠中引发有效的抗肿瘤免疫反应。