A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy.
A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy.
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DOI：
10.1038/sj.bjc.6602953
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发表时间：
2006-02-13
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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理想的癌症治疗应该既摧毁原发肿瘤，同时又教育免疫系统将肿瘤识别为外来肿瘤，以便也根除远处转移。光动力疗法（PDT）涉及静脉内施用光敏剂，然后用红光照射肿瘤，产生活性氧，最终通过凋亡和坏死引起血管关闭和肿瘤细胞死亡。PDT后由于急性炎症反应、肿瘤特异性抗原的产生和热休克蛋白的诱导而刺激抗肿瘤免疫。绿色荧光蛋白（GFP）被用作光学报告物以非侵入性地成像小鼠肿瘤的进展，并且此外，可以充当外来（水母）抗原。我们询问是否GFP表达肿瘤可用于监测荷瘤小鼠对PDT的反应，以及当用GFP转导非免疫原性肿瘤细胞系时，肿瘤反应是否不同。我们将RIF-1或RIF-1 EGFP（用逆转录病毒载体稳定转导）细胞注射到C3 H/HeN小鼠的腿部，细胞和肿瘤生长同样良好。我们使用苯并卟啉衍生物和短的药物-光间隔的PDT。RIF-1 EGFP的小鼠完全治愈和100%存活，而RIF-1野生型肿瘤全部复发。治愈的小鼠对RIF-1 EGFP细胞的再攻击具有抗性，并且野生型RIF-1细胞的再攻击生长显著较慢。当RIF-1 EGFP肿瘤被手术切除时，RIF-1 EGFP再激发生长也较慢，但没有排斥反应。当用空逆转录病毒载体转导RIF-1细胞时，肿瘤的PDT治愈率较低。在小鼠血清中存在针对EGFP的抗体表明EGFP可以作为外源抗原，然后PDT可以刺激长期记忆免疫应答。
The ideal cancer treatment should both destroy the primary tumour and at the same time educate the immune system to recognise the tumour as foreign so that distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the i.v. administration of photosensitisers followed by illumination of the tumour with red light producing reactive oxygen species that eventually cause vascular shutdown and tumour cell death by apoptosis and necrosis. Anti-tumour immunity is stimulated after PDT due to the acute inflammatory response, generation of tumour-specific antigens, and induction of heat-shock proteins. Green fluorescent protein (GFP) is used as an optical reporter to noninvasively image the progression of mouse tumours, and in addition, may act as a foreign (jellyfish) antigen. We asked whether GFP-expressing tumours could be used to monitor the response of tumour-bearing mice to PDT, and whether the tumour response differed when a nonimmunogenic tumour cell line was transduced with GFP. We injected RIF-1 or RIF-1 EGFP (stably transduced with a retroviral vector) cells in the leg of C3H/HeN mice and both the cells and tumour grew equally well. We used PDT with benzoporphyrin derivative and a short drug-light interval. There were complete cures and 100% mouse survival of RIF-1 EGFP while RIF-1 wild-type tumours all recurred. Cured mice were resistant to rechallenge with RIF-1 EGFP cells and a rechallenge with wild-type RIF-1 cells grew significantly slower. There was also slower RIF-1 EGFP rechallenge growth but no rejection when RIF-1 EGFP tumours were surgically removed. There was a low rate of PDT cure of tumours when RIF-1 cells were transduced with an empty retroviral vector. The presence of antibodies against EGFP in mouse serum suggests EGFP can act as a foreign antigen and PDT can then stimulate a long-term memory immune response.
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