Tumors are made of two main components: the cancer cells themselves and a surrounding support structure called stroma. The ratio between these two parts varies widely, but in many solid tumors, the non-cancerous support tissue can account for 50% or more of the total mass. That means a tumor is far from a simple ball of rogue cells. It’s a complex, disorganized tissue with its own blood supply, immune cells, scaffolding proteins, and a distinctly abnormal internal chemistry.
Cancer Cells and Stroma
The cancer cells are what define the tumor, but they don’t exist alone. They’re embedded in stroma, a mixture of connective tissue, blood vessels, and various non-cancerous cells that the tumor recruits and reshapes to support its growth. Pathologists use something called the tumor-stroma ratio to describe how much of a tumor is actual cancer versus supporting tissue. A cutoff of 50% stroma is commonly used: tumors with more stroma than cancer cells (“stroma-high”) tend to behave differently, and in some cancers like head and neck squamous cell carcinoma, a higher proportion of stroma is linked to worse outcomes.
This ratio matters because it means that when you look at a tumor under a microscope, you’re not seeing a uniform mass. You’re seeing islands or sheets of cancer cells woven through a dense network of support tissue that the tumor has essentially built for itself.
The Scaffolding That Holds It Together
The physical framework of a tumor is called the extracellular matrix, a mesh of proteins that gives the tissue its structure. The dominant protein in this mesh is collagen, particularly collagen types I and IV, which tumors produce in excess compared to healthy tissue. This overproduction creates a stiff, fibrous environment, a process closely related to fibrosis (the same kind of scarring you’d see in a damaged liver or lung).
Woven into this collagen network are other structural proteins like fibronectin and laminin, along with a basement membrane made of collagen IV, nidogen, and perlecan. In normal tissue, this architecture is orderly. In a tumor, it’s chaotic. The matrix gets remodeled constantly, becoming denser and stiffer in ways that actually help cancer cells move, invade surrounding tissue, and resist treatment.
Non-Cancer Cells Inside the Tumor
A surprising variety of normal cell types live within a tumor, recruited from surrounding tissue and the bloodstream. The most prominent are cancer-associated fibroblasts, which are the construction workers of the tumor. They build and remodel the extracellular matrix, change the mechanical properties of the tissue, influence blood vessel growth, and even help the tumor hide from the immune system. Fibroblasts come in multiple subtypes with different, sometimes opposing functions, which is part of why tumors are so hard to treat.
Immune cells are also abundant. T cells, B cells, natural killer cells, and macrophages all infiltrate the tumor mass. CD8+ T cells are the body’s primary cancer-killing cells. They can recognize and destroy cancer cells directly. But the tumor environment often suppresses their activity. Tumor-associated macrophages, which should be part of the body’s defense, frequently get reprogrammed to promote tumor growth instead, contributing to treatment resistance. Neutrophils, monocytes, and dendritic cells round out the immune population, and their behavior depends heavily on signals within the tumor environment. Whether any given immune cell is fighting the tumor or inadvertently helping it depends on the specific cues it receives.
Endothelial cells line the blood vessels threading through the tumor. Pericytes wrap around those vessels for structural support. Depending on where the tumor grows, fat cells and even nerve cells can also become part of the mix.
Blood Vessels That Don’t Work Properly
Tumors grow their own blood supply through a process called angiogenesis, but the vessels they build are structurally abnormal. Normal blood vessels run in relatively straight, organized lines. Tumor blood vessels are tortuous and convoluted, with irregular branching patterns. They’re also significantly larger in diameter than expected.
Perhaps most striking: research using high-magnification microscopy on melanoma patients found that roughly half of the blood vessels inside tumors had no blood flow at all. These non-functional vessels create pockets of the tumor that are poorly supplied with oxygen and nutrients, which paradoxically can make the tumor harder to treat because many therapies rely on blood flow to reach cancer cells.
An Acidic, High-Pressure Interior
The chemistry inside a tumor is distinctly different from normal tissue. Cancer cells rely heavily on a type of metabolism that produces large amounts of lactic acid, even when oxygen is available. This drives lactic acid concentrations in the tumor environment to 10 to 30 millimolar, far above normal levels. The result is a pH as low as 6.0 to 6.5, compared to the normal tissue pH of around 7.4. This acidity suppresses immune cell function, promotes invasion, and can reduce the effectiveness of certain treatments.
The physical pressure inside tumors is also abnormal. In healthy tissue, interstitial fluid pressure hovers near zero. Inside tumors, it ranges from 0 to 100 mmHg, with a typical median around 19 mmHg. This elevated pressure is caused by leaky blood vessels, poor lymphatic drainage, and the dense, compressed stroma. It acts as a barrier, pushing outward against incoming blood flow and making it harder for drugs to penetrate deep into the tumor.
How Benign Tumors Differ
Benign tumors share the basic blueprint of cancer cells plus stroma, but with key structural differences. They grow slowly as cohesive, expanding masses that stay put. Because of this slow, outward growth, the surrounding normal tissue gets compressed into a rim of connective tissue called a fibrous capsule. This capsule acts like a boundary, keeping the tumor contained and making surgical removal straightforward in most cases. Malignant tumors lack this neat border. They send fingers of cancerous tissue into surrounding structures, which is why clean surgical margins are so important in cancer surgery.
Blood Cancers: Tumors Without a Mass
Not all tumors form solid lumps. Blood cancers like leukemia involve the same basic principle of uncontrolled cell growth, but the malignant cells circulate through the bloodstream and accumulate in the bone marrow rather than forming a discrete mass. The bone marrow becomes the “tumor microenvironment” in these cases, with cancer cells crowding out normal blood-forming cells and interacting with the marrow’s own support cells. The result is less a physical structure and more a systemic takeover, which is why blood cancers produce symptoms like anemia and immune suppression rather than a lump you can feel.