A tumor is not a solid ball of cancer cells. It’s a complex mix of cancer cells, immune cells, connective tissue cells, blood vessels, structural proteins, and fluid. In many solid tumors, the cancer cells themselves may be outnumbered by the supporting cast of non-cancerous cells and materials that surround them. Understanding what fills that mass helps explain why tumors behave the way they do and why they can be so difficult to treat.
Cancer Cells Are Only Part of the Picture
The cancer cells are the defining feature of a tumor, but they exist within a busy neighborhood of other cell types collectively called the tumor microenvironment. This environment includes multiple types of immune cells (T cells, B cells, macrophages, and natural killer cells), specialized connective tissue cells called fibroblasts, and the cells that line blood vessels. All of these interact with the cancer cells, sometimes fighting the tumor and sometimes, paradoxically, helping it grow.
Every cancer cell carries its own set of DNA mutations, and no two cancer cells in the same tumor are necessarily identical. As cancer cells divide, they accumulate additional genetic errors over time. Some of these errors involve entire chunks of chromosomes being rearranged, deleted, or copied. This genetic diversity within a single tumor is one reason treatments can kill most of a tumor’s cells but leave behind a resistant population that regrows.
The Scaffolding That Holds It Together
Between the cells sits a dense web of proteins and sugars called the extracellular matrix. This network contains roughly 300 different molecules and serves as the physical scaffolding of the tumor. Its main structural proteins are collagen, fibronectin, and elastin, which connect cells to the surrounding tissue. A second layer, called the basement membrane, is a sheet-like structure made primarily of a different type of collagen and proteins called laminins that line the surfaces of blood vessels and tissue boundaries.
In tumors, this matrix is far from passive. Enzymes produced by immune cells and fibroblasts crosslink collagen fibers, stiffening the structure over time. The matrix also contains hyaluronan, a sugar-based molecule that absorbs water and causes the tissue to swell. This stiffened, swollen matrix does more than provide structure. It acts as a physical barrier that can block immune cells from penetrating into the tumor’s interior, essentially shielding cancer cells from the body’s defenses. It also traps fluid, raising the internal pressure of the tumor to 10 to 40 mmHg in many cancers, with some melanomas reaching pressures as high as 100 mmHg. Normal tissue pressure hovers near zero.
Fibroblasts: The Tumor’s Construction Crew
Fibroblasts are normally responsible for maintaining connective tissue throughout your body, producing collagen and helping with wound healing. Inside a tumor, they transform into what researchers call cancer-associated fibroblasts. These altered cells most likely originate from normal tissue-resident fibroblasts, though fat cells, blood vessel lining cells, and other cell types may also convert into them.
Cancer-associated fibroblasts are prolific multitaskers. They secrete growth factors and signaling molecules that promote tumor growth, remodel the surrounding tissue to make room for expansion, and support the formation of new blood vessels. They also create a protective niche around cancer cells that can shield them from chemotherapy and other treatments. Notably, these fibroblasts are a double-edged sword: some subtypes appear to restrain tumor growth rather than promote it, which complicates efforts to target them therapeutically.
Blood Vessels Unlike Any in Healthy Tissue
Tumors need oxygen and nutrients to grow, so they recruit their own blood supply. The primary way they do this is by releasing signaling proteins, most notably vascular endothelial growth factor (VEGF), which coax nearby blood vessels to sprout new branches toward the tumor. But tumors also acquire blood flow through other methods: hijacking existing blood vessels in the surrounding organ, recruiting stem cells from bone marrow to build new vessels, and in some aggressive cancers like melanoma, forming vessel-like channels out of cancer cells themselves without any normal blood vessel cells at all.
The resulting vasculature looks nothing like healthy blood vessels. Normal blood flow follows an orderly hierarchy: arteries branch into smaller arterioles, then into tiny capillaries, then into veins. Tumor vessels have no such organization. They are irregular in size, shape, and branching pattern, with no recognizable distinction between arterioles, capillaries, or veins. Even large-caliber tumor vessels often consist of little more than a thin lining of cells and a basement membrane, missing the muscular layers that give normal vessels their structure. Vessel density is highly uneven: the advancing edge of a tumor typically has four to ten times more blood vessels than the tumor’s interior, where the arrangement becomes chaotic. This haphazard plumbing means some tumor cells are well fed while others are starved.
The Immune Cells Inside
A tumor is heavily infiltrated with immune cells, and their composition tells a lot about how aggressive the cancer is and how well it might respond to treatment. The key players include killer T cells (CD8+ cells), which are among the most common immune cells in many tumors and are capable of directly destroying cancer cells. Helper T cells (CD4+ cells) coordinate the broader immune response. Natural killer cells provide a faster, less targeted form of attack. B cells, better known for producing antibodies, also infiltrate tumors and have been identified as a predictor of how well patients respond to certain therapies.
But the tumor fights back. Regulatory T cells, identifiable by specific protein markers on their surface, actively suppress anti-tumor immunity. Tumor-associated macrophages are among the most abundant immune cells in many tumors and can shift between a cancer-fighting state and an immunosuppressive state that protects the tumor. Immature immune cells called myeloid-derived suppressor cells also accumulate, further dampening the immune response. Together, these suppressive cells create a local environment where the immune system is present but largely neutralized.
What Happens at the Center
Because of the chaotic blood supply, the interior of a fast-growing tumor often receives too little oxygen and nutrients. The cells at the center begin to die in an uncontrolled process called necrosis. Aggressive tumors literally die from the inside out, leaving a core of dead and dying cells, cellular debris, and released fluid. This necrotic core is not just a byproduct of poor blood flow. Research published in the Proceedings of the National Academy of Sciences found that this process of internal death is linked to the spread of cancer. As the interior breaks down, surviving cancer cells near the necrotic zone can enter remodeled blood vessels and disseminate to distant sites.
How Benign Tumors Differ
Benign tumors contain many of the same basic materials, including their own cells, connective tissue, and blood vessels, but their organization is fundamentally different. Benign growths typically expand outward in a slow, even pattern, compressing the surrounding normal tissue into a well-defined border of fibrous material. This compressed zone acts like a capsule, keeping the tumor contained. Malignant tumors, by contrast, invade through tissue boundaries, lack clean borders, and send tendrils of cells into surrounding structures. Some tumors fall into an intermediate category: locally aggressive with disorganized growth patterns but a low tendency to spread to other organs.
The distinction matters because the composition of a tumor, not just its size, determines its behavior. A malignant tumor’s stiffened matrix, leaky vessels, suppressed immune cells, and genetically diverse cancer cell population all work together to make it resilient, adaptable, and capable of spreading. A benign mass, with its orderly structure and intact boundaries, is a fundamentally different entity even though it may look like a similar lump on a scan.