Mechanism of Tumor Angiogenesis
The vascular system provides oxygen and nutrients necessary for tissue health and growth. Formation of new blood vessels is controlled by a series of chemical signals. Unlike normal healthy tissues, cancer cells produce their own signals to initiate blood vessel production. By overriding the normal limits, cancer cells create an unlimited supply of nutrients that allows the tumor to grow uncontrollably.
Angiogenesis and Cancer
Angiogenesis is the process that allows for the uncontrolled growth and metastasis of tumors. Blood vessels transport the oxygen and nutrients needed by all tissues. Production of new blood vessels, or angiogenesis, is necessary for tissues to grow, especially for wound healing, fetal development and during the menstrual cycle. Angiogenesis is normally regulated by a cascade of chemical signals that stimulate the creation of new blood vessels. Cancer cells, however, are able to bypass the normal controls and initiate angiogenesis on their own. This ability is a key component allowing tumors to grow without limits and metastasize to other organs. Without angiogenesis, tumors could not grow larger than 2 millimeters
Angiogenesis begins with the release of angiogenic growth factors, according to the Angiogenesis Foundation. These proteins are released by tumors or injured tissues undergoing repair. The released growth factors diffuse into neighboring tissue and bind to receptors on the surface of existing blood vessels. The receptors activate endothelial cells, which send signals to the cell nucleus.
Migration Toward Tumor
The endothelial cells next produce enzymes that dissolve small holes in the basement membrane, a covering surrounding the blood vessel. The endothelial cells begin dividing, according to the Angiogenesis Foundation, and migrate through the enzyme-created holes in the basement membrane. Adhesion molecules called integrins pull the endothelial cells through the holes in the basement membrane, forming a sprout.
The sprout continues to grow and migrate toward the tumor. Enzymes called matrix metalloproteinases dissolve the tissues at the leading edge of the sprout to enable it to continue moving unobstructed. The tissue remolds around the growing sprout as it moves forward.
As the sprout reaches the tumor, the edges roll inward to form a tube. Separate tubes combine into loops to enable blood circulation. When the tube formation is completed, smooth muscle cells form to support the new blood vessels. The finishing step is the initiation of blood flow through the newly formed vessels.