In order to identify high-risk groups of patients with cancer, understanding the mechanisms of invasion and metastasis from the viewpoint of gene expression is required; in particular, the changes in gene expression as tumours gain the ability to metastasise. Using a rat model of metastatic colorectal cancer (CRC), we determined the expression profiles of CRC cells that metastasised to the liver and the lung. In the hepatopulmonary metastasis model, metastasising ability increased with successive transplanted cell line generations. No significant differences in cellular proliferation ability were seen between the original cell line and succeeding metastatic cell lines. Analysis using cDNA macroarray showed that metastasising ability was associated with increased expression of integrin β4, γ-catenin, Smad 7, Bax, Bcl-2, c-fos and TGF-α, and a particularly marked increased expression of TGF-β, PDGFb, Cdk4 and Rho B. Expression of both Rho GDIβ and Gelsolin was reduced. These results suggest that high metastasising ability does not derive from a single gene, but rather through accumulated changes in the expression of several different genes.

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