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. 2012 Dec;93(6):414-20.
doi: 10.1111/j.1365-2613.2012.00841.x.

Bilobar colorectal liver metastases: a new model for preclinical studies

Léon Maggiori  1 , Frédéric Bretagnol, Mathilde Wagner, Caroline Hatwell, Yves Panis
Affiliations

Bilobar colorectal liver metastases: a new model for preclinical studies

Léon Maggiori et al. Int J Exp Pathol. 2012 Dec.

Abstract

This study aimed to develop a new model of colorectal liver metastases (LM) in the rat. Both single macroscopic and multiple bilobar microscopic LM were investigated, as this closely resembled the human situation, before right hepatectomy was performed for 'single' right LM. The single macroscopic LM was elicited by direct injection of DHD/K12 colorectal cancer cells under the capsule of the median liver lobe in immunocompetent BDIX rats. The bilobar micrometastases were elicited by intraportal injection of DHD/K12 cells. A preliminary protocol was conducted to assess the dose of cells required to inject in to the portal vein, using 10(6) , 2 × 10(6) and 3 × 10(6) DHD/K12 cells (n = 15 rats). The resultant protocol for the experimental model used intraportal injection of 10(6) DHD/K12 cells and direct injections of 0.5 × 10(6) , 10(6) and 1.5 × 10(6) DHD/K12 cells (n = 15 rats). For both protocols, BDIX rats were sacrificed at day 30 after injection. The preliminary protocol showed that intraportal injection of 10(6) DHD/K12 cells was associated with bilobar micrometastases of 0.8 mm mean diameter at day 30. The main protocol assessed that direct injection of 0.5 × 10(6) under the liver median lobe capsule and intraportal injection of 10(6) DHD/K12 cells were associated at day 30 with a single macroscopic metastasis confined to a liver lobe and bilobar micrometastases, without peritoneal carcinomatosis or lung metastasis. Thus we have developed a new experimental model of bilobar colorectal LM including both macro- and microscopic colorectal LMs, which mimics the human situation and which will be useful in preclinical studies.

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Figures

Figure 1
Figure 1
Experimental model (right) and corresponding clinical situation (left): single macroscopic liver metastasis (black colour) and multiple diffuse micrometastases (grey colour).
Figure 2
Figure 2
Experimental workflow.
Figure 3
Figure 3
Optical microscopy of micrometastasis obtained 30 days after intraportal injection of 1 × 106 DHD/K12 cells (stain: haematoxylin–eosin–saffran).
Figure 4
Figure 4
Micrometastases diameter obtained 30 days after intraportal injection of 1 × 106 DHD/K12 cells, 2 × 106 DHD/K12 cells or 3 × 106 DHD/K12 cells and macrometastases diameter obtained 30 days after subcapsular injection of 0.5 × 106 DHD/K12 cells, 1 × 106 DHD/K12 cells or 1.5 × 106 DHD/K12 cells under the liver capsule of the median lobe.
Figure 5
Figure 5
Macrometastasis obtained 30 days after subcapsular injection of 0.5 × 106 DHD/K12 cells under the liver capsule of the median lobe. (a): Full liver specimen; (b): optical microscopy of macrometastasis (stain: haematoxylin–eosin–saffran).
See this image and copyright information in PMC

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