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自发性、侵袭性和转移性鼠乳腺癌细胞(TS/A—PC)可以通过逆转录病毒载体转染分泌鼠α_1-干扰素基因.几乎所有的分泌α_1-干扰素基因的TS/A细胞克隆(TS/A-IFN-α)在小鼠的生长受抑制,只能形成小的肿瘤,而单纯的TS/A细胞或仅转染对照细胞(I/A.TC)则能在皮下形成大的肿瘤结节,这种对肿瘤的抑制排斥主要能通过CD8~+T淋巴细胞和多形核细胞介导.为了在体内研究分泌不同细胞因子的肿瘤细胞的变异情况,作者选择了低免疫原性而肺高转移性的TS/A为肿瘤模型,利用电穿孔法将分泌α—干扰素的基因转染上述肿瘤细胞,分别对照了TS/A细胞、I/A.TC细胞,发现彼此间均未测到分泌IL-2、IL-4、IFN-r、IL-1-α;同时,分泌的α_1—干扰素在体外培养时对TS/A的增生无明显作用.皮下注射不同浓度的TS/A-IFN-α,均能延迟皮下肿瘤结节的形成,部分小鼠在皮下注射一个月后肿瘤结节完全消失,70%～90%接种肿瘤的动物存活期超过4个月,另一方面,在免疫抑制状态的BALB/c小鼠,同时用抗CD8抗体治疗时可以使TS/A-IFN-α细胞形成肿瘤结节的能力完全恢复.病理和超微结构显示,TS/A—PC和I/A.TC所致的肿瘤无坏死现象,外周有少量炎性细胞,而TS/A-IFN-α细胞形成的肿瘤外周有淋巴细胞和巨噬细胞浸润,中央坏死部分有新生细胞,有较多的成纤维组织和?
Spontaneous, invasive and metastatic murine breast cancer cells (TS/A-PC) can secrete murine α 1 -interferon genes by retroviral vector transfection. Almost all TS/A cell clones secreting α 1 -interferon genes (TS/A-IFN-α) is inhibited in mouse growth and can only form small tumors, whereas simple TS/A cells or only transfected control cells (I/A.TC) can form large subcutaneous tumors. The tumor nodules, which inhibit tumor rejection, are mainly mediated by CD8~+ T lymphocytes and polymorphonuclear cells. In order to study the variation of tumor cells secreting different cytokines in vivo, the authors chose a low immunogen. TS/A, a highly metastatic lung-derived metastatic model, was used as a tumor model to transfect the above-mentioned tumor cells with an electroporation method and to control TS/A cells and I/A.TC cells, respectively. No secretion of IL-2, IL-4, IFN-r, and IL-1-α was detected. At the same time, secreted α1-interferon had no apparent effect on the proliferation of TS/A in vitro. Subcutaneous injection of different concentrations TS/A-IFN-α can delay the formation of subcutaneous tumor nodules. In some mice, tumor nodules completely disappeared after subcutaneous injection for one month, 70% to 90%. The survival time of the animals of the tumor is more than 4 months. On the other hand, BALB/c mice in immunosuppressive state can completely make TS/A-IFN-α cells to form tumor nodules when treated with anti-CD8 antibody. Recovery, pathology and ultrastructure showed that tumors caused by TS/A-PC and I/A.TC showed no necrosis, and there were a small number of inflammatory cells in the periphery, whereas tumors formed by TS/A-IFN-α cells had peripheral lymphoid tissues. Infiltration of cells and macrophages, neonatal necrotic cells, new cells, there are more fibroblasts and?