Hematogenous metastasis is the process by which cancer cells from a primary tumor travel through the bloodstream to establish new tumors in distant parts of the body. This process is a significant factor in determining a patient’s prognosis and treatment, and it is fundamental to understanding cancer’s progression from a localized issue to a systemic disease.
The Initial Escape: Entering the Bloodstream
A tumor must first develop its own blood supply to grow, a process known as angiogenesis. These new vessels provide the tumor with nutrients and oxygen but are often leaky and poorly constructed. This makes them easier for cancer cells to penetrate in a process called intravasation, where a cell breaks away from the primary tumor and enters the bloodstream.
To achieve this, cancer cells become mobile and invasive. They detach from the tumor mass and degrade the basement membrane, a thin layer that encases the blood vessel. The cells produce enzymes that digest this barrier, creating an opening for the cancer cell to squeeze through the vessel’s lining and enter the bloodstream.
Surviving the Circulatory System
The bloodstream is a perilous environment for a cancer cell. It faces immense physical stress from the force of blood flow, known as shear stress, which can tear cells apart. The circulatory system is also patrolled by the immune system. Natural Killer (NK) cells are adapted to identify and destroy abnormal cells, including circulating tumor cells (CTCs), and the vast majority of cancer cells that enter the bloodstream are quickly destroyed.
To survive this journey, cancer cells have developed evasion strategies. A common tactic is to form a shield by interacting with blood platelets. Cancer cells produce proteins that cause platelets to clump around them, forming a micro-aggregate. This platelet cloak physically protects the cancer cell from fluid forces and also masks it from recognition by immune cells, allowing it to travel undetected.
Arrival and Exit: Lodging in a New Organ
The journey for a circulating tumor cell often ends when it becomes trapped in the narrow capillaries of a distant organ. These tiny blood vessels act as a filter. Once lodged, the cell must exit the bloodstream to invade the new tissue in a process called extravasation, the reverse of intravasation.
Extravasation begins with the cancer cell adhering firmly to the endothelial cells that form the inner lining of the blood vessel. The cell then secretes enzymes to digest the vessel’s basement membrane from the inside. It then pushes its way through the vessel wall and into the surrounding organ tissue.
Establishing a New Colony
Arriving in a new organ does not guarantee a new tumor, as most cancer cells that successfully extravasate die shortly after. The new tissue environment can be inhospitable, and many lone cells or small clusters, known as micrometastases, are eliminated by the local immune response or fail to adapt.
Some cells may enter a state of dormancy, remaining inactive for months or even years. For a new metastasis to form, a cancer cell must adapt to the new organ, evade local immune defenses, and proliferate. To grow into a clinically detectable secondary tumor, this new colony must once again induce angiogenesis to recruit its own blood supply.
Patterns of Spread: Why Cancer Favors Certain Organs
The distribution of metastases is not random, as certain cancers show a preference for specific organs. This phenomenon, known as organ tropism, is explained by two main factors. The first is the pattern of blood flow. For instance, blood from the colon flows directly to the liver, which helps explain why colorectal cancer frequently metastasizes there.
The second factor is the “seed and soil” hypothesis, which suggests that a cancer cell (the “seed”) must land in a compatible organ environment (the “soil”) to grow. Specific molecules on a cancer cell’s surface can act like a key, binding to “lock” molecules on the cells of a particular organ, facilitating invasion. This biological compatibility explains why breast cancer often spreads to the bone, lung, and liver, and why prostate cancer has a high affinity for bone.