Macrophages promote tumour growth and liver metastasis in an orthotopic syngeneic mouse model of colon cancer
Macrophages promote tumour growth and liver metastasis in an orthotopic syngeneic mouse model of colon cancer
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DOI：
10.1007/s00384-013-1703-z
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发表时间：
2013-10-01
影响因子：
2.8
通讯作者：
Partecke, L. I.
中科院分区：
文献类型：
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作者：
Kruse, J.;von Bernstorff, W.;Partecke, L. I.
肿瘤相关的巨噬细胞已被证明在几种癌中促进增殖、血管生成和转移。对结肠癌的影响尚未明确。此外，肝脏中的库普弗细胞可能通过直接结合肿瘤细胞而启动转移灶的形成。已经研究了结肠癌的原位同基因小鼠模型以及肝转移灶模型，使用Balb/c小鼠中的鼠CT-26结肠癌细胞。在两种模型中，大环内酯均被氯膦酸盐脂质体耗尽。使用7特斯拉MRI确定肿瘤大小和转移。原位肿瘤中的巨噬细胞和血管密度以及肝脏中的枯否细胞密度通过免疫组织化学进行评估。与对照组（683 +/- 389 mm（3），p = 0.0072）相比，巨噬细胞去除组的动物显示出显著更小的原发性肿瘤（37 +/- 20 mm（3））。耗尽组中没有小鼠显示肝或腹膜转移，而6只对照小鼠中有4只显示肝转移，6只小鼠中有5只显示腹膜转移。巨噬细胞耗竭组的血管密度显著较低（p = 0.0043）。在肝转移模型中，枯否细胞耗尽组的动物（14.3 +/- 7.7）显示出比两个对照组的小鼠显著更少的肝转移（PBS脂质体，118.5 +/- 28.2，p = 0.0117; NaCl，81.7 +/- 23.2，p = 0.0266）。肝转移的数量与枯否细胞密度直接相关（p = 0.0221）。在该原位同基因小鼠模型中，巨噬细胞促进肿瘤生长、血管生成和转移。枯否细胞促进肝转移瘤的形成。
Tumour-associated macrophages have been shown to promote proliferation, angiogenesis and metastasis in several carcinomas. The effect on colon cancer has not yet been clarified. Furthermore, Kupffer cells in the liver might initiate the formation of metastases by directly binding tumour cells.An orthotopic syngeneic mouse model of colon cancer as well as a liver metastases model has been studied, using murine CT-26 colon cancer cells in Balb/c-mice. Macrophages were depleted in both models by clodronate liposomes. Tumour sizes and metastases were determined using 7-Tesla MRI. The macrophage and vascular density in the orthotopic tumours as well as the Kupffer cell density in the livers were evaluated using immunohistochemistry.Animals in the macrophage-depleted group displayed significantly smaller primary tumours (37 +/- 20 mm(3)) compared to the control group (683 +/- 389 mm(3), p = 0.0072). None of the mice in the depleted group showed liver or peritoneal metastases, whereas four of six control mice displayed liver and five out of six mice peritoneal metastases. The vascular density was significantly lower in the macrophage-depleted group (p = 0.0043). In the liver metastases model, animals of the Kupffer cell-depleted group (14.3 +/- 7.7) showed significantly less liver metastases than mice of the two control groups (PBS liposomes, 118.5 +/- 28.2, p = 0.0117; NaCl, 81.7 +/- 23.2, p = 0.0266). The number of liver metastases correlated directly with the Kupffer cell density (p = 0.0221).Macrophages promote tumour growth, angiogenesis and metastases in this orthotopic syngeneic mouse model. Kupffer cells enhance the formation of metastases in the liver.