The challenge now is to use functional assays to identify those genes that play a role in metastasis. The complex process of tumor growth and metastasis can only be completely modelled in experimental animals. Using transplantable tumor cell line-based models, expression of candidate genes will be ectopically overexpressed by transfection or suppressed using RNAi in tissue cultured tumor cell lines.
The effect of the modified gene expression on tumor growth and metastasis will then be analysed by injecting the modified cells into syngeneic or immuno-suppressed animals as appropriate. Using genetically modified animal models, selected candidate genes will be either over-expressed using transgenesis, or expression of the gene will be ablated using targeted deletion. The modified mice will be bred onto backgrounds that develop tumors with a defined metastatic proclivity. The effect of the genetic modification of the germline on tumor growth and metastasis will then be assessed. These animal models will also be used for testing novel experimental anti-cancer therapies.