Anti-Metastatic Benefits Produced by Hyperthermia and a CCL3 Derivative
Anti-Metastatic Benefits Produced by Hyperthermia and a CCL3 Derivative
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DOI：
10.3390/cancers11111770
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发表时间：
2019-11-01
期刊：
影响因子：
5.2
通讯作者：
Takahashi, Akihisa
中科院分区：
文献类型：
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作者：
Ma, Liqiu;Kambe, Ryosuke;Takahashi, Akihisa
大量恶性肿瘤细胞已经扩散到周围组织和其他远处器官，这些细胞往往太小，无法在诊断测试中发现，即使是这样小的转移，预防也应该改善患者的预后。在小鼠模型中，我们在这篇文章中表明，在局部轻度高温后静脉给药携带单个氨基酸替代的人CCL3变体不仅可以诱导肿瘤在治疗部位的生长抑制，还可以抑制转移。将Colon26腺癌细胞（1 × 10(5)个细胞/只）皮下移植到同基因BALB/c小鼠右后腿，9天后，当肿瘤大小达到直径约11 mm时，局部肿瘤肿块暴露于高频波下，瘤内温度在42℃下保持30分钟。小鼠在热处理后第1天开始连续5天静脉注射名为eMIP的CCL3变体（2 μ g/只/天）。我们发现，热疗后eMIP受者的肿瘤生长明显受到抑制，但在单独接受热疗或eMIP治疗的动物中没有发现任何影响。此外，与所有其他对照相比，接受联合治疗的动物在高温治疗后18天评估的肺转移数量显着减少。这些结果鼓励这种联合疗法在未来的临床应用。
Significant numbers of malignant tumor cells that have spread to surrounding tissues and other distant organs are often too small to be picked up in a diagnostic test, and prevention of even such small metastases should improve patient outcomes. Using a mouse model, we show in this article that intravenous administration of a human CCL3 variant carrying a single amino acid substitution after mild local hyperthermia not only induces tumor growth inhibition at the treated site but also inhibits metastasis. Colon26 adenocarcinoma cells (1 x 10(5) cells/mouse) were grafted subcutaneously into the right hind leg of syngeneic BALB/c mice and after nine days, when tumor size reached similar to 11 mm in diameter, the local tumor mass was exposed to high-frequency waves, by which intratumoral temperature was maintained at 42 degrees C for 30 min. Mice received the CCL3 variant named eMIP (2 mu g/mouse/day) intravenously for five consecutive days starting one day after heat treatment. We found that tumor growth in eMIP recipients after hyperthermia was inhibited markedly but no effect was seen in animals treated with either hyperthermia or eMIP alone. Furthermore, the number of lung metastases evaluated at 18 days after hyperthermia treatment was dramatically reduced in animals receiving the combination therapy compared with all other controls. These results encourage future clinical application of this combination therapy.