title: Macrophages promote tumour growth and liver metastasis in an orthotopic syngeneic mouse model of colon cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Macrophages promote tumour growth, angiogenesis and metastases in this orthotopic syngeneic mouse model. Kupffer cells enhance the formation of metastases in the liver.
authors: Department of General, Visceral, Thoracic and Vascular Surgery, University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, 17475, Greifswald, Germany.
authors: J
authors: J
authors: Kruse
authors: W
authors: W
authors: von Bernstorff
authors: K
authors: K
authors: Evert
authors: N
authors: N
authors: Albers
authors: S
authors: S
authors: Hadlich
authors: S
authors: S
authors: Hagemann
authors: C
authors: C
authors: Günther
authors: N
authors: N
authors: van Rooijen
authors: C-D
authors: CD
authors: Heidecke
authors: L I
authors: LI
authors: Partecke
mesh_terms: D000818:Animals; D002452:Cell Count; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000098:blood supply / Q000473:pathology*; D004195:Disease Models, Animal; D007728:Kupffer Cells / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary*; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation
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