What is a Metastasis and Why, How, and Where Do They Happen

Definition and Importance of Metastases With Cancer

diagram of caner cells spreading through tissue
What is the meaning of the term metastasis?. istockphoto.com

A metastasis refers to the spread of cancer cells from their primary location (the organ in which the cancer began) to another region of the body. Cancer cells may spread through the bloodstream, the lymphatic vessels, or locally, and can do so because chemicals that ordinarily keep cells where they belong in the body are absent. Cancers can metastasize to nearly any regions of the body, but some of the more common sites are the bones, lungs, liver, and brain. Symptoms are often related to the presence of cancer cells in the organ where they spread. The treatment of metastases can vary with the original cancer and the region to which it has spread. Understanding metastases is a critical area of cancer research, as metastatic disease is responsible for roughly 90 percent of cancer deaths.

Metastasis: Definitions

As noted, "metastasis" is the word used to describe a cluster of cancer cells in one area that arose from a cancer in another region of the body. Cancer that has spread in this way is called metastatic cancer. Metastatic cancer is named based on the site where the cancer began. For example, if lung cancer spreads to the bones, it would not be called “bone cancer” but rather “lung cancer metastatic to the bones.” In this case, when the metastatic cells are looked at under the microscope they would be cancerous lung cells, not bone cells.

Some cancers are metastatic at the time of diagnosis, while others become metastatic after the cancer has progressed, or recurs. When a cancer is gone (or at least is unable to be detected by scans) and then later recurs at a site away from the original cancer, it is termed a "distant recurrence." In staging cancers, a tumor that has metastasized is usually considered stage 4.

Importance of Metastases

The ability to metastasize is one major characteristic that distinguishes malignant (cancerous) tumors from benign (non-cancerous) tumors. Some benign tumors can grow to be quite large, and cause significant problems, especially if they are in an enclosed space such as the brain. Yet these tumors do not spread to other regions of the body. 

Metastases are responsible for 90 percent of cancer deaths, and therefore significant research is in progress looking at both ways to treat metastases and ways to prevent this spread from occurring in the first place.     

Why Do Cancers Spread? 

Normal cells do not spread beyond the area where they belong. For example, lung cells do not travel to the heart even though they are nearby. The reason for this is that normal cells have "adhesion chemicals" that act somewhat like glue, that keep the different cells together in their area of origin. Lacking these adhesion chemicals, cancer cells that break off from a tumor are "loose" and mobile, and free to travel if they should reach the lymphatic vessels or bloodstream (see below). Another difference is that normal cells communicate with other nearby cells—in essence, being reminded of their boundaries. Cancer cells have devised ways to ignore these communication signals, so they can travel locally and penetrate into nearby tissues. There are other differences between cancer cells and normal cells that allow the cancer cells that have traveled to set up residence in a new location.

How Do Cancers Metastasize (Spread)?

  • Locally (regionally): When benign tumors grow they do so as a solid mass, as if there is a clear boundary containing them. In contrast, cancer cells invade neighboring tissues in an invasive manner which can appear like tentacles. It is, in fact, the claw-like extension of cancer into other tissues from which the name originates; cancer being derived from the Greek word for claw or crab.
  • Through the bloodstream: Cancer cells can enter the bloodstream and travel to other regions of the body.
  • Through the lymphatic system: The lymphatic system is another network through which cancer cells can travel.
  • Through the airways (lung cancer): In addition to the methods of metastasis above, recent studies suggest that lung cancer, likely spreads through the airway of the lungs (aerogenous metastasis) as well, and this may be even more important than bloodstream metastasis for people with lung adenocarcinoma.

Once a cancer has spread, further steps are needed to ensure the cancer cells can continue to grow. One necessity is the formation of new blood vessels to feed the new tumor, a process called angiogenesis. Medications called angiogenesis inhibitors work to interrupt this process, making it difficult for tumors to establish themselves in new areas.

Where do Cancers Spread?

Most cancers have the ability to spread to any region of the body, but some sites of metastases are more common than others.

  • The most common sites of metastasis overall include the bones, liver, and lungs.
  • The most common sites for breast cancer to metastasize are the bones, the brain, the liver, and the lungs.
  • The most common sites for lung cancer to spread are the adrenal glands, the bones, the brain, the liver, and elsewhere in the lungs. 
  • The most common sites for colon cancer to metastasize are the liver, the lungs, and the peritoneum (the membranes lining the abdominal cavity).
  • The most common distant sites to which prostate cancer spreads are the adrenal glands, the bone, the liver, and the lungs.

Symptoms of Metastases

Symptoms of metastatic cancer can include those related to the presence of tumor in a particular area of the body to which a cancer has spread, as well as non-specific symptoms such as unintentional weight loss and fatigue. Some symptoms may include:

  • Lung metastases may cause a persistent cough, shortness of breath, or chest pain.
  • Brain metastases may cause headaches, vision loss, seizures, numbness or weakness of the arms or legs, and loss of balance.
  • Bone metastases may cause pain in the region where the affected bone is located, as well as an elevated calcium level in the blood (hypercalcemia of malignancy.) When cancer is present in a bone it can be more likely to fracture, and the first sign of a bone metastasis may be a pathologic fracture (fracture through a bone damaged by a tumor.) When cancer spreads to the spine, it may cause spinal cord compression with resulting weakness of the legs and bowel or bladder dysfunction.
  • Liver metastases may cause jaundice (a yellow discoloration of the skin,) bloating, abdominal pain, and weight loss.
  • Metastases to the adrenal gland are often asymptomatic but important with regard to treatment.

Treatment of Metastatic Cancer

The treatment of metastatic cancer will depend upon the location of the primary tumor. Metastatic cancer cannot usually be cured, but it is treatable. Newer medications such as targeted therapies and immunotherapy are improving the survival rates for some people with metastatic cancer, and several medications are being studied in clinical trials which bring hope that further improvements in metastatic cancer treatment are near.

Some areas of metastases are, however, more difficult to treat than others. Due to a complex network of tightly knit cells referred to as the blood brain barrier, a barrier designed to prevent toxins from gaining access to the central nervous system, many chemotherapy drugs, and some targeted therapies are unable to reach areas of metastases in the brain. Studies are in progress looking at medications which are better able to penetrate into the brain, as well as other methods of treating these metastases. 

For some people who have one or only a few sites of metastases (oligometastases,) removing the metastasis with surgery or radiation may improve survival. The term metastasectomy is used to describe the removal of metastases and may be considered with some types of cancer with only a few metastases to the brain, liver, or lung.

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