There is a gene called C-Met which is involved in cell migration. This is particularly dangerous in cancer patients as it means that cancer cells can spread more quickly and easily. In colon cancer patients, death occurs after the tumour has spread, causing metastasis. C-Met isn't a gene that is normally active in colon cells, but it can be activated by the cancer. This research program is going to examine how much impact the C-Met gene has on cancer spreading, and therefore how important it is in the control and treatment of cancer.

Death from colon cancer is due to spread of tumour to the liver (metastasis). Genetic changes during the development of cancer leads to over- expression of normal genes not usually expressed in colonic cancer cells. One of these, C- Met, is associated with cell migration and may be an important contributor to metastasis. By manipulating the levels of C- Met in colon cancer cells we can access the contribution of this gene to the process of metastasis using the vivo models.

Aims and Objectives

1. Create human and mouse colon cancer cell lines with either over expression of C- Met or under expression of C- Met (by expression of antisense or dominant negative allele).
2. Determine the effects of modulating C- Met levels on the invasive and metastatic potential of colon tumour cells using both in vitro and the following in vivo models:
   
   a) The effect of C- Met on primary tumour growth following subcutaneous inoculation of tumour cells.
   b) Effect of C- Met on the establishment and growth of hepatic metastasis following splenic subcapsular inoculation of tumour cells (cells enter the circulation from the spleen and are trapped in the capillary bed of the liver).
   c) Effect of C- Met on lung colony formation following IV injection of tumour cells (cells are trapped in the capillary bed of the lung).

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