What is metastasis?

by Barbara Christie-Pope, PhD
Professor of Biology, Cornell College

Metastasis is the movement of cancer cells from a primary tumor to a distant site in the body. This simple definition does not capture the fear and devastation felt by an individual when they learn that they have metastatic disease. The initial reaction is, why did this happen? Why didn’t my therapy work? I thought I was “cancer-free”; how could this come back to haunt me ten years later? Is there something I did that caused this? The questions are endless and sometimes overwhelming.

Unfortunately, these questions lack answers. Around 90% of all cancer mortality is due to metastasis; therefore, research is necessary to treat metastatic disease and to prevent metastasis in the first place. The mechanisms underlying the development of metastatic tumors, often referred to as the metastatic cascade, is poorly understood but many avenues of research are piecing together the route tumor cells must travel to new sites in the body and, once there, how these cells respond to their new, foreign environment.

The cascade begins when a cell from the primary tumor detaches and enters the lymph circulation and on to the blood or enters the blood directly. This process requires the cells to navigate through the blood vessel wall, travel through the blood, then exit the blood vessel to gain entry to tissues. Tumor cells in the blood are met with a very hostile physical and cellular environment. These cells enter a fast-flowing river where they encounter obstacles such as the inner banks of the blood vessel wall. The shearing forces and pressure within the blood vessel can damage their fragile cell walls. Cells of the immune system are also found in blood. These natural killer cells are appropriately named and have the ability to recognize the tumor cells and destroy them. Unfortunately, platelets, small fragments of cells involved in blood clotting, can form a protective barrier around the tumor cells allowing survival and assisting with the exit of the tumor cells into the tissue surrounding the blood vessel.

Although thousands of cells may begin this arduous journey, few actually survive. This sounds like good news. But unfortunately, it only takes one seeding cell to begin the new formation of a secondary tumor.

In addition, these disseminated tumor cells, or DTCs, usually begin this cascade prior to detection of the primary tumor. Once leaving the blood and entering another tissue or organ, DTCs encounter a new environment, the so-called microenvironment, which contributes to and may determine their survival, their ability to stop multiplying and remain quiescent or dormant, and their resistance to therapy.

But, if cancer therapy is systemic or administered all over the body, how do DTCs escape this therapy only to revive and begin multiplying into a secondary tumor years to decades later? Because most cancer therapies target rapidly dividing cells, non-dividing DTCs are resistant to these therapies. We need strategies to target DTCs by either keeping them dormant and stopping their reactivation or destroying them. Current research is identifying the factors including proteins and genes that determine and regulate the interactions between DTCs and the environment surrounding them. Therapies that target these interactions could conceivably halt the recurrence of cancer. Unfortunately, there are no tests to determine where DTCs are in the body; therefore, it is challenging to determine whether or not an individual will experience metastatic disease.

DTCs are ticking time-bombs. Defusing these bombs is going to take more research and is a major therapeutic challenge. Want to find out more about how researchers are working to prevent or stop metastasis and death from cancer? On Tuesday, October 19, 2021, from 5:30-8:30 via zoom, Beyond Pink TEAM will feature Dr. Cyrus Ghajar, whose groundbreaking research into dormant cancer cells and the environments within which they may awaken is one of the most promising new developments in cancer research. Dr. Ghajar studies how the microenvironments within distant tissues regulate DTC dormancy and/or growth. He believes that solving these puzzles will allow the development of drugs that eradicate dormant DTCs before they can develop into full-blown metastases. He conducts this work within the Fred Hutchinson Cancer Center Laboratory for the Study of Metastatic Microenvironments.
​Register for the Ignite the Cancer Conversation event here.


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