What is angiogenesis?

Relation of angiogenesis to cancer. In one way, a cancerous tumor is like any other bodily structure: its survival depends on the provision of oxygen and nutrients and the removal of waste. Cancerous tumors differ from normal tissue in that they tend to spread, or metastasize, without regard for normal borders between different tissues such as muscle, cartilage, and bone. Blood supply to a tumor enables it to spread. For its support and ability to grow, the cancer must in effect persuade the body to build vessels to and throughout the tumor, something that seems counterintuitive. In fact, the body contains defenses against this. As cancer develops, however, these defenses are short-circuited.

The way the tumor fools its host into cooperation is chemically, with proteins and enzymes found naturally in the body but used by the tumor to its advantage. Proteins that induce growth are known as growth factors. Researchers have shown evidence that one chemical secreted by tumors, vascular endothelial growth factor (VEGF), in effect attracts blood vessels. Induced by growth factors and possibly hormones, new blood vessels actually sprout from existing vascular tracts into and around the cancer. Researchers also report that breast cancer cells produce interleukin-8 (IL-8), a protein that normally attracts white blood cells to injuries and inflammation but is also known to be angiogenic.

Other researchers, exploring the role of certain enzymes in regulating angiogenesis in breast cancer, are focusing on the extracellular matrix, noncellular material that surrounds any tissue (picture the stuffing around mattress springs) and is common to both normal tissues and tumor cells. In addition to taking up space between cells (including cartilage, tendon, ligament, and bone), the extracellular matrix performs a critical function. Under normal circumstances after adulthood, the extracellular matrix prevents unauthorized (non-injury-related) angiogenesis and cell movement. Cancer short-circuits that inhibitory function. Compared with normal breast cells, some breast cancer cells have higher levels of certain enzymes that degrade heparan sulfate, an important component of the extracellular matrix. A weakened and degraded extracellular matrix might well enable abnormal cell movement and angiogenesis.

Preventing cancer-related angiogenesis: If tumors require angiogenesis to survive and spread, then it seems logical to discourage angiogenesis. Inhibitors of angiogenesis were first discovered in 1975 and since then have been detected in such diverse natural sources as tree bark, green tea, fungi, shark cartilage and muscle, sea coral, and various herbs. Potential methods to prevent or change the process of angiogenesis include blocking the chemical signals from the tumor, making these signals less effective; preventing the breaching of the extracellular matrix; and, after a tumor has already been supplied with blood vessels, causing the vessels to normalize, or stop supplying the tumor.

A number of angiogenesis inhibitors have been approved for use by the US Food and Drug Administration (FDA), most of which work by blocking VEGF. While promising, these drugs are still largely experimental, in part because of the complexity and diversity of the tumors themselves. What works for one tumor may not work for another. Another complication of agents that inhibit angiogenesis is the chaos they could produce in inflammation control and healing. Nevertheless, the possibility of inhibiting angiogenesis only where it is needed, with very targeted inhibitors and perhaps with the assistance of other drugs such as paclitaxel (Taxol) and cyclophosphamide (Cytoxan, Neosar) and such cyclooxygenase-2 (COX-2) inhibitors as celecoxib (Celebrex) and thalidomide, all of which interfere with angiogenesis, remains an attractive investigative path. Research and clinical trials are ongoing.

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