Angiogenesis

by National Cancer Institute

What Is Metastasis?

When patients are diagnosed with cancer, they want to know whether their disease is local or has spread to other locations. Cancer spreads by metastasis, the ability of cancer cells to penetrate into lymphatic and blood vessels, circulate through the bloodstream, and then invade and grow in normal tissues elsewhere.

In large measure, it is this ability to spread to other tissues and organs that makes cancer a potentially life-threatening disease, so there is great interest in understanding what makes metastasis possible for a cancerous tumor.

Metastasis Requires Angiogenesis

Cancer researchers studying the conditions necessary for cancer metastasis have discovered that one of the critical events required is the growth of a new network of blood vessels. This process of forming new blood vessels is called angiogenesis.

What Is Tumor Angiogenesis?

Tumor angiogenesis is the proliferation of a network of blood vessels that penetrates into cancerous growths, supplying nutrients and oxygen and removing waste products. Tumor angiogenesis actually starts with cancerous tumor cells releasing molecules that send signals to surrounding normal host tissue. This signaling activates certain genes in the host tissue that, in turn, make proteins to encourage growth of new blood vessels.

Normal Angiogenesis in Children

In addition to its role in tumors, angiogenesis occurs normally in the human body at specific times in development and growth. For example, a developing child in a mother's womb must create the vast network of arteries, veins, and capillaries that are found in the human body. A process called vasculogenesis creates the primary network of vascular endothelial cells that will become major blood vessels. Later on, angiogenesis remodels this network into the small new blood vessels or capillaries that complete the child's circulatory system.

Normal Angiogenesis in Adults

Proliferation of new blood vessels also takes place in adults, although it is a relatively infrequent event. In women, angiogenesis is active a few days each month as new blood vessels form in the lining of the uterus during the menstrual cycle. Also, angiogenesis is necessary for the repair or regeneration of tissue during wound healing.

Angiogenesis and Vascular Endothelial Cells

The walls of blood vessels are formed by vascular endothelial cells. These cells rarely divide, doing so only about once every 3 years on average. However, when the situation requires it, angiogenesis can stimulate them to divide.

Angiogenesis and Regulatory Proteins

Angiogenesis is regulated by both activator and inhibitor molecules. Normally, the inhibitors predominate, blocking growth. Should a need for new blood vessels arise, angiogenesis activators increase in number and inhibitors decrease. This prompts the growth and division of vascular endothelial cells and, ultimately, the formation of new blood vessels.

Angiogenesis and Cancer

Before the 1960s, cancer researchers believed that the blood supply reached tumors simply because pre-existing blood vessels dilated. But later experiments showed that angiogenesis - the growth of the new blood vessels - is necessary for cancerous tumors to keep growing and spreading.

Without Angiogenesis, Tumor Growth Stops

In early experiments, researchers asked whether cancer growth requires angiogenesis. Scientists removed a cancerous tumor from a laboratory animal and injected some of the cancer cells into a normal organ removed from the same strain of animal. The organ was then placed in a glass chamber and a nutrient solution was pumped into the organ to keep it alive for a week or two. Scientists found that the cancer cells grew into tiny tumors but failed to link up to the organ's blood vessels. As a result, tumor growth stopped at a diameter of about 1-2mm. Without angiogenesis, tumor growth stopped.

With Angiogenesis, Tumor Growth Proceeds

In another experiment designed to find out whether cancer growth can continue when angiogenesis occurs, researchers compared the behavior of cancer cells in two regions of the same organ. Both locations in the eye had nutrients available, but only one could support angiogenesis. Scientists found that the same starting injection of cancer cells grew to 1-2mm in diameter and then stopped in the region without nearby blood vessels, but grew well beyond 2 mm when placed in the area where angiogenesis was possible. With angiogenesis, tumor growth continued.

What Prompts Angiogenesis?

In an experiment designed to find out whether molecules from the cancer cells or from the surrounding host tissues are responsible for starting angiogenesis, scientists implanted cancer cells in a chamber bounded by a membrane with pores too small for the cells to exit. Under these conditions, angiogenesis still began in the region surrounding the implant. Small activator molecules produced by the cancer cells must have passed out of the chamber and signaled angiogenesis in the surrounding tissue.

About the Author

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