Mechanisms

Metastasis occurs because tumour cells acquire an increased degree of autonomy:

• increased cellular motility
• less contact inhibition of growth and less adhesiveness between tumour cells
• abnormal interaction with components of extracellular matrix
• secretion of proteolytic enzymes to create a space in advance of tumour cells

Enzymes such as metalloproteinases have a vital role in the progression through blood vessels. This is a relatively inefficient process as even large tumours will yield only a few haematogenous metastases every day. The tumour cells then circulate as an embolus within the circulation. It is at this point that regulation by lymphoid cells can occur: natural killer cells and macrophages can destroy tumour cells directly whereas cytotoxic T-cells require the presence of an antigen coating the tumour cell. If the tumour cells survive, they may adhere to a basement membrane at a distant site and then invade locally. The location at which they settle is thought to be partly dependent on the anatomical location of the primary tumour and on the cell surface properties of the metastases.