The majority of deaths (about 90%) associated with cancer are due to the metastasis of the original tumor cells to sites distant from the initial or primary tumor. Metastasis is the process by which cancer cells migrate throughout the body.
In order for cells to move through the body, they must first climb over/around neighboring cells. They do this by rearranging their cytoskeleton and attaching to the other cells and the extracellular matrix via proteins on the outside of their plasma membranes. By extending part of the cell forward and letting go at the back end, the cells can migrate forward. The cells can crawl until they hit a blockage which cannot be bypassed. Often this block is a thick layer of proteins and glycoproteins surrounding the tissues, called the basal lamina or basement membrane. In order to cross this layer, cancer cells secrete a mixture of digestive enzymes that degrade the proteins in the basal lamina and allow them to crawl through.
The proteins secreted by cancer cells contain a group of enzymes called matrix metalloproteases (MMP). These enzymes act as ‘molecular scissors’ to cut through the proteins that inhibit the movement of the migrating cancer cells. Once the cells have traversed the basal lamina, they can spread through the body in several ways. They can enter the bloodstream by squeezing between the cells that make up the blood vessels.
Once in the blood stream, the cells float through the circulatory system until they find a suitable location to settle and re-enter the tissues. The cells can then begin to grow in this new location, forming a new tumor.
The process of metastasis formation is very inefficient process but leads to the majority of deaths associated with cancer. This is because the number of cells that leave a tumor can be in the millions per day. Even if only a small fraction of the cells that leave a tumor are able to survive to form a new tumor, the large number of attempts means that a distant growth is likely to occur at some point
Migrating cancer cells can die from a variety of causes, including:
- Cells normally live tightly connected to their neighbors and the meshwork of proteins surrounding them. Detachment from the surface of other cells can lead to cell death (called anoikis ‘an-oh-e-kus’).
- Cancer cells are often quite large in comparison to the cells that normally live in the lymphatic system or blood system. When they travel through the vessels they can get damaged or stuck, leading to cell death.
- Cancer cells can be recognized and destroyed by cells of the immune system
Additionally, it is important to note that even if a cancer cell does not die, it does not mean that it will form a tumor. The cells may exist at locations far from the original tumor without multiplying enough to cause any problems.
The process of metastasis is shown in the video below.
Watch Emory Winship Cancer Institute Researcher Adam Marcus describe his research on cancer metastasis. Contains actual video of cancer cells moving.
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