How cancer spreads: the biology of metastasis

Cells in a malignant tumour will be accumulating new mutations with each life-cycle, or cell division. This means that there will be different types of cells within the one tumour. We say, that there are therefore 'heterogenous' populations of cells within the one tumour. These populations are all organised in a way that supports tumour growth. Some cells will be stimulating the formation of new blood vessels so as to guarantee nutrition; some will be making growth-factor hormones to stimulate a greater rate of cell division etc.

The switch that occurs for a malignant tumour to become metastatic begins with a few cells that acquire the ability to detach and move away from the primary cancer: through the extracellular matrix and invade the circulation.

This subpopulation of cells which detach from the primary tumour mass, migrate through the surrounding cell matrix and into the bloodstream are the metastasising population of tumour cells: the cells that are spreading the cancer. In the bloodstream, most of these cells die due to 'anoikis' (lack of support the cell had while attached to the tumour environment), or from abrasion or immune system attack. However, those that survive are responsible for the potential spread of cancer and can grow to form metastases. These cells are called 'Circulating Tumour Cells,' often abbreviated to 'CTCs.'

These cells may survive in a dormant state within the circulation for months or years until a certain environmental trigger stimulates their exit from the bloodstream. This quiescent state is called 'clinical cancer dormancy,' and may last up to ten years. They may remain in a dormant state, even after exiting the blood, until the microenvironment prompts them to grow again.

At the point of dissemination, the CTCs will exit from the blood stream and settle in an organ or body part that may be foreign to where it came from. The CTC will have all the information necessary for initiating and maintaining the growth of a new tumour at the new site. This information is coded in the mutations which it has accumulated over many life cycles. The information will include such things as how to attach to a new type of surrounding organ; how to stimulate the organ to release growth factors that stimulate growth of cells and blood vessels etc.

It is cancer metastasis, rather than the primary cancer, that is the main cause of cancer-related death.

General public: A great video explanation by Harvard University can be found here
Practitioners: A great review entitled Biology, detection and clinical utility of Circulating Tumor Cells by Pantel et. al, is available free from Pubmed Central