Anti-tumor effects of the bacterium Caulobacter crescentus in murine tumor models
Anti-tumor effects of the bacterium Caulobacter crescentus in murine tumor models
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DOI：
10.4161/cbt.5.5.2553
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发表时间：
2006-05-01
影响因子：
3.6
通讯作者：
Suresh, M. R.
中科院分区：
文献类型：
--
作者：
Bhatnagar, P. K.;Awasthi, A.;Suresh, M. R.
新月柄杆菌是一种革兰氏阴性、非致病性细菌，常见于水生和土壤环境中。值得注意的一个特征是由单一蛋白质组成的蛋白质表面层（S层），组织为包裹细菌的自组装晶体阵列。在努力将癌症相关肽作为基因插入表达到S层的过程中，我们注意到未修饰细菌的肿瘤抑制作用。C.检测crescentus对三种可移植肿瘤小鼠模型的抗肿瘤活性：C57 BL/6中用MUC 1基因转染的刘易斯肺癌细胞、BALB/c中的鼠乳腺癌（EMT-6）（预防和治疗模式）和DBA 2中的鼠白血病细胞（L1210）。用C. p.免疫小鼠三次。crescentus（2 × 10（7）个细胞/小鼠）。在预防模式中，在最后一次免疫后两周用肿瘤细胞攻击小鼠。活C.与盐水对照组相比，Crescentus在所有三种可移植肿瘤模型中产生抗肿瘤活性，如通过延长的存活、减少的肿瘤质量或减少的肺结节数量所测量的。在刘易斯肺和EMT-6乳腺癌小鼠模型中，用C.新月形，与对照组相比;对于EMT-6，这在预防和治疗模式中观察到。在小鼠白血病和刘易斯肺癌模型中，在用柄杆菌免疫的小鼠组中观察到延长的存活。在大多数情况下，C。Crescentus细胞明显比热灭活或福尔马林固定的细胞更有效，尽管它们在小鼠中不生长或不存留。结果表明，C. Crescentus可能是一种安全的细菌免疫调节剂，用于治疗肿瘤。
Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in aquatic and soil environments. One feature of note is a protein surface layer (S-layer) composed of a single protein, organized as a self-assembled crystalline array that coats the bacterium. In the course of efforts to express cancer-associated peptides as genetic insertions into the S-layer, we noted a tumor suppressive effect of the unmodified bacterium. C. crescentus was examined for anti-tumor activity against three transplantable tumor mouse models: Lewis lung carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary carcinoma (EMT-6) in BALB/c ( both in prophylactic and therapeutic mode) and murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with C. crescentus (2 x 10(7) cells/mouse). In prophylactic mode, the mice were challenged with tumor cells two weeks after the last immunization. Immunization with live C. crescentus resulted in anti-tumor activity in all three transplantable tumor models, as measured by prolonged survival, reduced tumor mass or reduced number of lung nodules, compared to saline control groups. In the Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung nodules as well as the tumor weight was lower in mice treated with C. crescentus, compared to the control group; for EMT-6, this was observed in prophylactic and therapeutic modes. In the murine leukemia and Lewis lung carcinoma models prolonged survival was observed in the groups of mice immunized with Caulobacters. In most cases the live C. crescentus cells were markedly more efficacious than heat killed or formalin fixed cells, despite the fact that they do not grow or persist in mice. The results suggest that C. crescentus may be a safe, bacterial immunomodulator for the treatment of tumors.