How Does Cancer Spread to Other Parts of the Body?
How Does Cancer Spread to Other Parts of the Body?
Cancer spreads when some cells leave the original tumor, invade nearby tissue, enter blood or lymphatic vessels, travel through the body, and establish growth in another organ. This process is called metastasis. It is difficult and inefficient: most cancer cells that leave a tumor do not form a new tumor. Successful metastasis requires cells to survive several separate biological barriers.
By Chris Morais, MSc, MPhil, PhD
- What Is Metastasis?
- Why Is Metastasis Different From the Original Tumor Growing Larger?
- How Do Cancer Cells Break Away From the Primary Tumor?
- How Do Cancer Cells Invade Nearby Tissue?
- How Do Cancer Cells Enter Blood or Lymphatic Vessels?
- How Do Cancer Cells Survive While Traveling Through the Body?
- How Do Cancer Cells Leave Blood Vessels and Enter a New Tissue?
- Why Do Cancer Cells Spread to Some Organs More Often Than Others?
- How Does a Metastatic Cancer Cell Establish a New Tumor?
- Do All Cancer Cells Have the Ability to Metastasize?
- Can Cancer Cells Spread Before the Primary Tumor Is Found?
What Is Metastasis?
Metastasis is the spread of cancer cells from the primary site where the disease began to a distant part of the body, forming a secondary tumor of the same cancer type [1].
The original cancer is called the primary tumor, while a tumor that develops at a distant site is called a metastatic tumor [1]. A metastatic tumor remains the same biological type of cancer as the original primary mass:
- Preserved identity: Kidney cancer that spreads to the lung is metastatic kidney cancer, not lung cancer.
- Shared characteristics: The cells in the secondary organ came directly from the primary tumor and retain important biological features of the original cancer.
Metastasis is not a single event. Cells must complete a multi-step journey known as the metastatic cascade [2]. To form a new tumor, cancer cells must invade surrounding tissue, enter the circulation, survive transport, reach another organ, penetrate its tissue, survive in that foreign environment, and establish sustained growth [2].
Each stage acts as a significant physical and biological barrier. Large numbers of cancer cells may shed from a primary tumor, but only a small fraction survive long enough and find suitable conditions to establish a secondary tumor.
Why Is Metastasis Different From the Original Tumor Growing Larger?
A primary tumor grows larger by continuous cell division at its original site, whereas metastasis requires cells to break away, travel through circulation, and colonize an entirely new organ [2].
A growing primary tumor often expands directly into neighboring tissues through local invasion. For example, a tumor may grow through its normal organ boundary into an adjacent structure. While this makes the cancer locally invasive, local invasion alone is not distant metastasis.
| Feature | Primary Tumor Growth | Metastatic Spread |
|---|---|---|
| Location | Arises at the original site and may invade nearby tissues | Spreads to and colonizes distant organs |
| Spread Pattern | Expands locally and may invade neighboring structures | Enters blood or lymph vessels to travel systemically |
| Cellular Ability | Sustained proliferation within the primary tumor | Detachment, circulation survival, and foreign adaptation [2] |
| Biological Hurdles | Expanding within a familiar local microenvironment | Overcoming multiple bodily barriers in foreign tissue |
| Efficiency | Generally more efficient than metastatic spread; successful cell division enlarges the local mass | Highly inefficient; only a small fraction of disseminated cells eventually form metastases |
The abilities required for metastasis are partly separate from rapid proliferation. A cancer cell that multiplies rapidly inside a primary tumor may fail to survive in the bloodstream or adapt to another organ. Conversely, some cells develop traits that favor movement and survival but remain unable to colonize distant tissue. This difference explains why primary tumor size and metastatic spread do not always progress together in a simple, predictable way.
How Do Cancer Cells Break Away From the Primary Tumor?
Cancer cells break away from a primary tumor when changes in cell adhesion, cell shape, and local tissue signaling reduce the physical bonds that hold them in place.
Normal epithelial cells stay firmly attached to neighboring cells and rest on an organized structural base called the basement membrane. Cancer disrupts the specific proteins and signaling pathways that maintain these attachments:
- Epithelial–mesenchymal plasticity: Some carcinoma cells undergo changes known as epithelial–mesenchymal plasticity, often discussed in connection with the epithelial–mesenchymal transition (EMT) [2]. Cells decrease typical epithelial traits, loosen cell-to-cell bonds, alter their shape, and become mobile [2].
- Hybrid states: Cancer cells rarely undergo a complete, permanent switch from epithelial to mesenchymal states; many occupy flexible intermediate states that shift with changing conditions.
- Collective invasion: Cancer cells do not always break away as isolated single units. Groups of cells can stay connected and move together through collective invasion, later entering the circulation as multi-cell clusters.
- Microenvironment signals: Local fibroblasts, immune cells, blood vessel cells, extracellular matrix components, and low oxygen levels (hypoxia) actively influence how easily cancer cells detach.
How Do Cancer Cells Invade Nearby Tissue?
Cancer cells invade nearby tissue by breaching the basement membrane and using mechanical forces, flexible shape changes, and remodeling enzymes to move through surrounding material [2].
The basement membrane is a dense, organized layer of extracellular proteins separating epithelial tissues from deeper connective tissue. Crossing this barrier is the first physical step required for local tissue invasion.
To move forward, cancer cells alter their grip on the surrounding matrix, generate internal physical force, alter their shape to pass through tight spaces, and release enzymes to clear pathways through the tissue [2].
How Do Cancer Cells Move Through the Extracellular Matrix?
The extracellular matrix (ECM) is a structural network of proteins—such as collagen, laminins, fibronectin, and proteoglycans—surrounding living cells. Cancer cells move through this matrix using several coordinated mechanisms:
- Integrin attachment: Cancer cells use surface adhesion molecules called integrins to grip extracellular matrix proteins.
- Cytoskeletal traction: The internal actin cytoskeleton generates mechanical pulling and pushing forces that draw the cell forward.
- Enzymatic remodeling: Cancer cells and surrounding stromal cells release digestive enzymes, including matrix metalloproteinases (MMPs), to break down matrix proteins and carve out migration paths.
- Cellular squeezing: Some cancer cells migrate without heavy matrix breakdown by altering their shape to squeeze through pre-existing matrix gaps.
Matrix structure also actively directs invasion. Increased tissue stiffness, reoriented collagen fibers, and structural tracks laid down by stromal cells help steer the direction and speed of advancing cancer cells.
How Do Cancer Cells Enter Blood or Lymphatic Vessels?
Cancer cells enter blood or lymphatic vessels through a process called intravasation, crossing the vessel wall to access systemic transport.
After invading local tissue, cancer cells reach microvessels and cross their endothelial barrier:
- Entry through abnormal blood vessels: Tumor blood vessels can have loose endothelial junctions and abnormal supporting structures, which may make some regions easier for cancer cells to penetrate.
- Microenvironmental cooperation: Perivascular immune cells, particularly macrophages, can exchange molecular signals with cancer cells and endothelial cells that increase vessel permeability and assist entry [2].
- Entry through lymphatic vessels: The thin walls and specialized endothelial structure of local lymphatic vessels provide an alternate dissemination route.
Cells entering the lymphatic system are carried to regional lymph nodes, where some remain and grow. Others pass through the nodes to reach the general bloodstream. The balance between blood and lymphatic spread differs among cancer types, and the route taken varies between individual tumors [3].
Entering blood or lymphatic circulation is a major route to distant dissemination, but vascular entry does not guarantee that a cell will successfully colonize a distant organ.
How Do Cancer Cells Survive While Traveling Through the Body?
Some circulating tumor cells survive transit by resisting detachment-induced cell death (anoikis), while others may gain survival advantages by traveling in clusters or interacting with blood platelets [2], [4].
Once inside the bloodstream, circulating tumor cells (CTCs) leave behind their supportive solid tissue and enter a hostile environment marked by mechanical fluid shear stress, immune attack, and rapid changes in oxygen and nutrient availability [2], [4].
- Resisting anoikis: Detachment from the extracellular matrix triggers a natural self-destruction process in normal epithelial cells called anoikis. Metastatic cancer cells can resist this process through altered survival signaling.
- Traveling in clusters: While many cells travel individually, some circulate as CTC clusters composed of two or more tumor cells. These clusters sometimes include non-cancerous cells like platelets, immune cells, or stromal cells. Remaining attached to other cells can preserve survival signals, reduce anoikis, and increase metastatic potential [4].
- Platelet shielding: Platelets can stick to circulating tumor cells and may help shield them from immune attack and mechanical stress.
Despite these adaptations, circulation remains a severe biological bottleneck: most circulating cancer cells do not go on to establish metastatic tumors, and many die during transit or after reaching a distant site.
Cells moving through the lymphatic system experience slower flow and lower physical pressure than in the bloodstream, but they must still survive transport, evade immune defenses, and navigate lymph nodes.
How Do Cancer Cells Leave Blood Vessels and Enter a New Tissue?
Cancer cells leave the bloodstream through extravasation, a process where they arrest in distant microvessels, bind to the vessel wall, and cross into foreign tissue.
- Vessel arrest: Circulating cells often slow down or become physically trapped in narrow capillaries. However, physical size alone does not govern arrest; cancer cells can also form adhesive interactions with molecules on the endothelial surface [2].
- Endothelial crossing: The arrested cell attaches to the vascular lining and passes between or directly through endothelial cells. Local inflammation and loosened endothelial junctions can make this barrier easier to cross.
- Basement membrane penetration: The cancer cell breaks through the vessel’s outer basement membrane to enter the organ tissue.
Extravasation is not simply intravasation in reverse. The cell must interact with unfamiliar endothelial cells and extracellular matrix components in a new tissue bed, where local microenvironmental cues differ from those at the primary tumor.
A cell that successfully penetrates the new tissue is termed a disseminated tumor cell. Crossing into the organ still does not guarantee a metastatic tumor will form; the cell must adapt to the new microenvironment to survive.
Why Do Cancer Cells Spread to Some Organs More Often Than Others?
Cancer spread is non-random: tumors display metastatic organotropism, favoring specific target organs based on anatomical blood flow routes and local tissue compatibility [5].
Colorectal cancers frequently spread to the liver, while other cancers show marked preferences for bone, lungs, brain, or other specific sites. These patterns are influenced by where circulation carries cancer cells and whether the destination tissue provides conditions that support their survival and growth.
Does Blood Flow Help Determine Where Cancer Spreads?
Blood flow routes determine which capillary beds circulating cells encounter first.
- Portal circulation: Blood leaving the intestinal tract travels directly to the liver via the portal vein before returning to the heart. This physical route contributes to the liver being one of the most common sites of distant metastasis in colorectal cancer.
- Venous circulation: Many cancer cells entering the systemic venous circulation pass through the right side of the heart and then encounter the capillary networks of the lungs.
Anatomy creates the initial physical opportunity, but blood flow alone cannot explain metastatic patterns. Cancer cells circulate through many organs where tumors never develop, and some well-perfused organs are rarely colonized [5]. Successful metastasis requires biological compatibility beyond simple physical trapping.
Why Does the New Tissue Environment Matter?
A disseminated cancer cell enters a foreign environment with distinct cell types, nutrients, extracellular matrix proteins, growth factors, and immune defenses.
- The "Seed and Soil" hypothesis: This relationship is captured by the classical seed and soil principle: the cancer cell acts as the seed, and the distant organ serves as the soil. A seed can land in many places, but it grows only where the soil provides supportive conditions.
- Local cell interactions: Resident fibroblasts, immune cells, endothelial cells, and extracellular matrix proteins determine whether a newly arrived cell dies, stays dormant, or grows [5].
- The pre-metastatic niche: Some primary tumors release systemic signals and extracellular vesicles through the circulation that prepare distant organs ahead of time. These signals can remodel local blood vessels, recruit immune cells, and alter the matrix, helping create a more supportive pre-metastatic niche before cancer cells arrive.
How Does a Metastatic Cancer Cell Establish a New Tumor?
A metastatic cancer cell establishes a new tumor through metastatic colonization, which requires it to adapt to the foreign tissue, survive local immune defenses, and secure continued access to oxygen and nutrients [2].
Colonization is a major biological bottleneck and is often considered a rate-limiting phase of the metastatic cascade [2]:
- Micrometastasis formation: A disseminated cell that adapts to local nutrient and matrix conditions begins to divide, forming a microscopic cluster of cancer cells called a micrometastasis.
- Vascular recruitment: To expand beyond a microscopic cluster, the growing secondary tumor must secure continuing oxygen and nutrients by stimulating new blood vessel growth (angiogenesis) or tapping into existing host vessels.
- Metastatic dormancy: Some disseminated cells enter a dormant state and remain alive without actively dividing. Small metastatic deposits can also remain clinically dormant when their overall growth is held in check [2].
Dormant cells can persist in tissues for months or years. Later changes in immune function, tissue architecture, matrix remodeling, or local signaling can reawaken these dormant cells, triggering delayed metastatic growth.
Do All Cancer Cells Have the Ability to Metastasize?
No. Cancer cells within the same tumor differ substantially, and only a small fraction successfully completes all stages of metastasis. Metastatic ability is not necessarily confined to one fixed rare cell type; cancer cells can change their functional state, undergo selection, and cooperate with other cells as the disease evolves [2], [4].
Tumors contain biologically and genetically diverse cellular populations. One cell may divide rapidly but lack invasive motility; another may invade local tissue but fail to survive circulation shear forces; a third may reach a distant organ but lack the machinery to survive foreign tissue conditions [2].
- Cellular plasticity: Cancer cells alter their functional states in response to changing local signals. A cellular state that facilitates detachment from the primary tumor may differ from the state required to establish a colony in distant tissue.
- Clonal evolution: Cells harboring mutations or traits that confer survival advantages during invasion, transit, or foreign arrest are selected over time.
- Cellular cooperation: Cancer cells often rely on non-cancerous partners. Interacting with platelets, local fibroblasts, and perivascular macrophages provides critical support at specific stages of the cascade [4].
Successful metastasis is not driven by a single gene or isolated behavior; it requires a combination of cellular traits matching the specific microenvironments the cell encounters.
Can Cancer Cells Spread Before the Primary Tumor Is Found?
Yes. In some cancers, cells can disseminate before the primary tumor is detected. Some of these disseminated cells may then remain dormant in distant tissues for long periods [1], [2].
Early dissemination does not mean a secondary tumor appears immediately. Disseminated cells may stay dormant as microscopic deposits for years before local signals trigger renewed cell division. This latency can help explain why metastatic recurrences sometimes arise long after a primary tumor was surgically removed or treated.
- Cancer of Unknown Primary (CUP): In some instances, metastatic tumors are diagnosed before the original primary tumor is identified. Occasionally, even comprehensive clinical testing cannot locate the original starting site, a condition classified as cancer of unknown primary [1].
- Tumor size versus spread: Although larger primary tumors may have more opportunities to release cancer cells, tumor size alone does not dictate whether spread has occurred. In some cancers, even small or early-stage tumors can disseminate cells.
The central distinction remains between cellular dissemination and successful metastasis: a cancer cell can leave the primary tumor early, but forming a clinically evident metastatic tumor requires surviving every barrier along the metastatic cascade.
Morais C. How Does Cancer Spread to Other Parts of the Body? [Internet]. BiologyWithin.com; 2026 Sep 13. Available from: https://www.biologywithin.com/2026/09/how-cancer-spreads-metastasis.html
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Chris is a biologist dedicated to making complex biological and physiological sciences clear, rigorous, and accessible.
Disclaimer: This article is for general educational purposes only and does not constitute medical advice, diagnosis, or treatment. Consult a qualified healthcare professional about personal health concerns.
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