When tumors develop, they require a supply of oxygen and nutrients for rapid growth and survival. To meet this demand, tumors induce the formation of their own blood vessel network, distinct from the body’s healthy vasculature. This specialized and often abnormal network is known as tumor vasculature, and its presence is fundamental to cancer progression and sustenance.
Understanding Tumor Vasculature
Tumor vasculature is the network of blood vessels that develops within and around a tumor, providing nourishment. These vessels differ considerably from healthy blood vessels. Tumor vessels are often characterized by their irregular structure, disorganized, tortuous, and inconsistent diameters. They may also contain abnormal bulges and blind ends, lacking the typical hierarchical arrangement of arterioles, capillaries, and venules seen in normal circulation.
A key characteristic of tumor blood vessels is their increased permeability, making them leaky. This leakiness results from gaps between endothelial cells, which are the cells lining the blood vessels, and an abnormal basement membrane. Increased permeability leads to fluid and plasma proteins accumulating in the surrounding tissue, contributing to elevated interstitial fluid pressure. This abnormal structure and impaired integrity distinguish tumor vessels from healthy ones, impacting tumor growth and treatment delivery.
How Tumor Blood Vessels Form (Angiogenesis)
The formation of new blood vessels, a process called angiogenesis, is used by tumors to establish their own blood supply. This process is triggered by a lack of oxygen (hypoxia) within the tumor. As a tumor expands, cells in its core become deprived of oxygen and nutrients because the existing blood supply cannot keep pace with metabolic demands.
In response to this hypoxic environment, tumor cells release specific signaling molecules, most notably Vascular Endothelial Growth Factor (VEGF). VEGF binds to receptors on the endothelial cells of nearby healthy blood vessels, stimulating them to proliferate, migrate, and form new sprouts towards the tumor. This intricate signaling pathway, involving VEGF and its receptor VEGFR-2, orchestrates the sprouting and branching of new vessels, enabling the tumor to draw in resources for expansion.
The Critical Role of Tumor Vasculature in Cancer Progression
The abnormal blood supply provided by tumor vasculature is highly beneficial for the tumor’s survival and progression. These newly formed vessels deliver oxygen and nutrients, such as glucose, essential for proliferation and metabolic activity of cancer cells. The vasculature also removes metabolic waste products, preventing their accumulation to toxic levels.
Beyond sustenance, tumor vasculature provides a direct route for cancer cells to spread throughout the body, a process called metastasis. The leaky and disorganized nature of these vessels allows tumor cells to enter the bloodstream from the primary tumor and travel to distant organs, forming new tumors. The irregular structure and impaired blood flow within the tumor vessels also create challenges for cancer treatment by hindering the delivery of chemotherapy drugs and immune cells to the tumor site, reducing treatment efficacy.
Targeting Tumor Vasculature in Cancer Treatment
Targeting tumor vasculature is a therapeutic strategy known as anti-angiogenic therapy, which aims to inhibit tumor growth by disrupting its blood supply. This approach aims to starve the tumor of oxygen and nutrients needed for growth and survival. By cutting off this supply, anti-angiogenic therapies can slow tumor progression or cause tumor shrinkage.
These therapies often work by blocking the signaling pathways responsible for angiogenesis, such as those involving VEGF or its receptors. For example, some drugs are designed to bind to VEGF, preventing it from stimulating new blood vessel growth. While anti-angiogenic therapies show promise in certain cancers, they face challenges such as the development of drug resistance by tumors or various side effects. Despite these hurdles, research continues to explore new ways to enhance treatment effectiveness, including combination therapies and strategies aimed at normalizing tumor vessels.