Metastasis is the process by which cancer cells spread from their original location, known as the primary tumor, to other parts of the body, forming new tumors. This spread represents a significant progression in cancer, moving beyond a localized disease.
The Journey of Cancer Spread
The journey of cancer spread, often called the metastatic cascade, involves a series of distinct, sequential steps that allow cancer cells to travel and establish new growths. Cells initially grow into or invade nearby healthy tissue, a process known as local invasion.
During local invasion, cancer cells can secrete enzymes, such as matrix metalloproteinases (MMPs), which degrade the surrounding extracellular matrix and basement membranes. This degradation creates pathways for the cells to move through the tissue. Cancer cells may also undergo a transformation called epithelial-mesenchymal transition (EMT), where they lose cell-to-cell adhesion and gain migratory capabilities, similar to mesenchymal cells that are designed for movement.
Following local invasion, the cancer cells enter the bloodstream or lymphatic vessels in a process called intravasation. This entry can occur actively, where cells migrate into vessels, or passively, such as when trauma to the primary tumor forces cells into circulation. Cancer cells interact with endothelial cells lining the vessels and use adhesion molecules like selectins and integrins to breach the vessel wall.
Once inside the circulatory or lymphatic system, these cancer cells become circulating tumor cells (CTCs). The circulation phase is challenging for CTCs, as most of them die due to shear stress from blood flow and attacks from immune cells, such as natural killer cells. However, a small fraction of these cells can survive, sometimes by forming clusters with other cell types like platelets or immune cells, which may offer protection.
The next step is extravasation, where CTCs exit the vessels at a distant location. This process often involves the CTCs adhering to the inner lining of small blood vessels, particularly capillaries, at the new site. They then form protrusions and squeeze through small openings in the vessel walls, eventually invading the surrounding tissue.
Finally, the extravasated cancer cells begin to proliferate and establish a new tumor, a process called colonization. This stage is often considered the most inefficient part of metastasis, as many disseminated cells fail to form detectable new tumors. Successful colonization requires the cells to adapt to the new microenvironment and often involves stimulating the growth of new blood vessels, a process called angiogenesis, to supply the developing secondary tumor.
Common Destinations of Metastasis
Cancer cells can spread to nearly any part of the body, but certain organs are more frequently affected. The most common sites where cancer metastasizes are the bones, liver, and lungs. Other common locations include the brain, lymph nodes, and sometimes the skin or adrenal glands.
The specific destination of metastasis often depends on the type of primary cancer. For example, breast cancer frequently spreads to the bones, brain, liver, and lungs. Colorectal cancer commonly metastasizes to the liver and lungs, while prostate cancer often spreads to the bones.
These organs are frequently affected because they have a rich blood supply, which makes it easier for circulating tumor cells to lodge there. The microenvironment within these organs, including the presence of specific growth factors and cell types, can also provide a hospitable “soil” for the cancer cells to establish and grow. For instance, bones offer a fertile ground due to constant cell turnover and the release of substances that can promote cancer growth.
Why Metastasis Matters Clinically
The presence of metastasis carries important clinical implications for individuals with cancer. It indicates a more advanced stage of the disease, often classified as Stage IV in systems like the TNM (Tumor, Node, Metastasis) staging system.
When cancer has metastasized, it means the disease is more widespread and complex to manage. While some metastatic cancers, such as certain melanomas or colon cancers, might be curable, many metastatic cancers are not, and treatment goals shift towards controlling the disease, managing symptoms, and extending life. Metastasis is a major factor in cancer-related deaths, accounting for approximately 90% of fatalities.
The presence and location of metastatic tumors directly influence treatment strategies. Treatments for metastatic cancer are systemic, meaning they affect the entire body, such as chemotherapy, immunotherapy, or targeted therapy. The treatment approach for a metastatic tumor is based on the characteristics of the primary cancer, not the organ where the metastasis is found; for example, breast cancer that has spread to the liver is still treated as metastatic breast cancer.
Diagnosing Metastasis
Healthcare professionals employ various methods to detect metastasis. Imaging techniques are used to visualize internal structures and identify suspicious lesions. These include computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, and positron emission tomography (PET) scans.
Bone scans are used to detect cancer that has spread to the bones, while ultrasound may also be used depending on the suspected site of spread. These imaging modalities help determine the extent of the disease and pinpoint new tumor formations. For instance, PET/CT scans offer whole-body images and provide metabolic information about tumor tissue.
In addition to imaging, biopsies of suspicious lesions are performed to confirm metastasis. A biopsy involves taking a tissue sample from the suspected secondary tumor for microscopic examination and analysis. This allows pathologists to determine if the cells in the new lesion match the characteristics of the primary cancer, confirming its metastatic origin. Blood tests, which can include tumor marker-based tests, may also provide additional information by detecting substances produced by cancer cells or by the body in response to cancer.