Chen Y-L, Wang C-Y, Yang F-Y, Wang B-S, Chen J Y, Lin L-T, Leu J-D, Chiu S-J, Chen F-D, Lee Y-J, Chen W R
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
Department of Radiotherapy, Cheng Hsin General Hospital, Taipei, Taiwan.
Cell Death Dis. 2014 Apr 17;5(4):e1178. doi: 10.1038/cddis.2014.159.
Stimulation of the host immune system is crucial in cancer treatment. In particular, nonspecific immunotherapies, when combined with other traditional therapies such as radiation and chemotherapy, may induce immunity against primary and metastatic tumors. In this study, we demonstrate that a novel, non-toxic immunoadjuvant, glycated chitosan (GC), decreases the motility and invasion of mammalian breast cancer cells in vitro and in vivo. Lung metastatic ratios were reduced in 4T1 tumor-bearing mice when intratumoral GC injection was combined with local high-intensity focused ultrasound (HIFU) treatment. We postulate that this treatment modality stimulates the host immune system to combat cancer cells, as macrophage accumulation in tumor lesions was detected after GC-HIFU treatment. In addition, plasma collected from GC-HIFU-treated tumor-bearing mice exhibited tumor-specific cytotoxicity. We also investigated the effect of GC on epithelial-mesenchymal transition-related markers. Our results showed that GC decreased the expression of Twist-1 and Slug, proto-oncogenes commonly implicated in metastasis. Epithelial-cadherin, which is regulated by these genes, was also upregulated. Taken together, our current data suggest that GC alone can reduce cancer cell motility and invasion, whereas GC-HIFU treatment can induce immune responses to suppress tumor metastasis in vivo.
刺激宿主免疫系统在癌症治疗中至关重要。特别是，非特异性免疫疗法与放疗和化疗等其他传统疗法联合使用时，可能会诱导针对原发性和转移性肿瘤的免疫反应。在本研究中，我们证明了一种新型无毒免疫佐剂——糖化壳聚糖（GC），在体外和体内均可降低哺乳动物乳腺癌细胞的运动性和侵袭性。当瘤内注射GC与局部高强度聚焦超声（HIFU）治疗联合应用时，4T1荷瘤小鼠的肺转移率降低。我们推测这种治疗方式刺激宿主免疫系统对抗癌细胞，因为在GC-HIFU治疗后检测到肿瘤病灶中有巨噬细胞聚集。此外，从接受GC-HIFU治疗的荷瘤小鼠采集的血浆表现出肿瘤特异性细胞毒性。我们还研究了GC对上皮-间质转化相关标志物的影响。我们的结果表明，GC降低了Twist-1和Slug的表达，这两种原癌基因通常与转移有关。受这些基因调控的上皮钙黏蛋白也上调。综上所述，我们目前的数据表明，单独使用GC可降低癌细胞的运动性和侵袭性，而GC-HIFU治疗可诱导免疫反应以抑制体内肿瘤转移。
