Table 1.
Evolution of in vivo studies examining early stages of colorectal cancer liver metastasis
| Reference | Strain of animal | Cancer cell line | Molecular target (intervention) | Labelling method | Tumour inoculation | Outcomes |
|---|---|---|---|---|---|---|
| Luzzi et al. (1998) | C57BL/6 mice | B16F1 murinemelanoma | NONE (none) | Fluoresbrite carboxylated polystyrene nanospheres | Superior mesenteric vein | Adhesion and extravasation process is very efficient (>80%survive). The inefficiency of metastatic process occurs after this early stage. |
| Naumov et al. (1999) | SCID mice | CHO-K1 | NONE (none) | GFP | Mesenteric vein | GFP expressing cells enables the metastatic process to be monitored in vivo. |
| Ito et al. (2001) | Athymic nude miceof KSN strain | Rat tongue carcinoma RSC3 LM and E2 | NONE (none) | GFP | Intra portal via mesenteric vein | Metastatic cells and non-metastatic cells arrest in hepatic circulation. After 3 days all non-metastatic cells cleared from liver. |
| Ding et al. (2001) | BALB/c mice – P selectin knockout mice and wild type C57BL/6 | C26 adenocarcinoma and EL-4 lymphoma | Selectins (function blocking mAb) | PKH-26 | Mesenteric vein | Colorectal cancer cells demonstrated mechanical entrapment. Lymphoma cells metastasized although these cells were smaller than the sinusoid diameter. Cell specific adhesions using P selectin are involved. |
| Kikkawa et al. (2002) | BALB/c mice | CHO-K1 | αvβ3 (cells transfected with αvβ3) | GFP | Portal vein andtail vein | Transfected αvβ3 showed significantly higher accumulation in the liver postportal vein injection but not in the lung after tail vein injection. |
| Reinmuth et al. (2003) | BALB/c mice | Murine CT26 adenocarcinoma | αvβ3 and αvβ5 (S247 and αvβ3/αvβ5 antagonist) | None | Spleen | S247 prolonged survival in this animal model. S247 impaired both metastatic and angiogenic processes. |
| Steinbauer et al. (2003) | BALB/c mice – SCID and wild type | Murine CT26 adenocarcinoma | NONE (none) | GFP and calcein AM | Portal vein | GFP stain in longer experiments can trigger an immune reaction. |
| Sturm et al. (2003) | BALB/c mice | Murine CT26 adenocarcinoma | NONE (none) | GFP | Spleen | Created an animal model for color ectal cancer using murine cancer cells in a murine host. |
| Haier et al. (2003) | Sprague–Dawley rats | Human HT29 and rat CC531 colorectal cancer cells | NONE (none) | Calcein AM | Intra-arterially, intravenous and extrahepatic portal vein | Created animal model without GFP label, which could cause immune reaction. Showed despite method of colorectal cancer cell inoculation, cells still metastasized to liver. |
| Enns et al. (2004) | Sprague–Dawley rats | Human HT29 cells (HT29P and HT29LMM) | Integrins –α1, α3, α5, α6, β4 and α2β1. VCAM-1 and Selectins | Calcein AM | Intra cardiac | Specific integrins play a key role in colorectal cancer cell adhesion to the liver and in tumour migration. ECM of space of Disse is important in metastasis formation. |
| Enns et al. (2005) | Sprague–Dawley rats | Human HT29 colorectal cancer cells | Intergins pan αv, αvβ3 and αvβ5 | Calcein AM | Intra-arterial | αv integrins especially αvβ5 have a key role in colorectal cancer cell adhesion to the liver. |
| Schluter et al. (2006) | Sprague–Dawley or nude rats | HT29P low, KM-12C Intermediate or HT29LMM, KM-12L4 colorectal cancer cells | Calcein AM | Intra-arterial | Cell adhesion occurred in metastatic target organs only. Migration into target organs correlated with their metastatic potential. |