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Salem Health: Cancer Angiogenesis Category: Cancer biology Also Known As: Blood vessel formation Definition Angiogenesis is the formation of new blood vessels. It is a perfectly normal process in a developing or growing body, and during a woman's reproductive years, it enables the menses and pregnancy. In addition, angiogenesis maintains health by developing a new blood supply in injured tissue, controlling inflammation, and even healing fractures of the bone. In health, the body controls angiogenesis, but in cancer, the body loses control. Angiogenesis is thought to be a process by which a cancer obtains its blood supply from its host. Without vascularization--the provision of blood vessels--no tissue in the body can live. Nearly every cancer known is associated with pathological 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 to 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, in effect the cancer must 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 which 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 common not only to normal tissues but also to 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 two enzymes that degrade heparin, an important component of the extracellular matrix. A weakened and degraded extracellular matrix might well enable abnormal cell movement and angiogenesis. Not every researcher, however, is convinced that tumors depend on angiogenesis. Citing the "immature" vasculature of some tumors--meaning that the blood vessels are not as well organized as in normal body tissues--and the lack of consistent evidence from clinical trials, they question cancer's angiogenesis dependency. Those who support the connection counter that cancer growth is by its very nature not only disorganized--it is growing a tumor rather than a kidney or a pancreas--but also, relative to other tissues, new in origin. Because cancer's growth, unlike that of healthy tissue, is continual, its vasculature might be expected to remain immature. Preventing Cancer-related Angiogenesis If tumors do 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. Ways to prevent or change the process of angiogenesis being investigated 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. Another area being researched targets oncogenes, genes that cause normal cells to become cancerous and also, it is believed, activate the angiogenesis switch. Researchers are developing antioncogene drugs. Angiogenesis inhibitors, while promising, have yet to be proven as efficacious treatments, 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 and cyclophosphamide and such COX-2 inhibitors as celecoxib and thalidomide, all of which interfere with angiogenesis, remains an attractive investigative path. Research and clinical trials are ongoing. Jackie Dial, Ph.D. For Further InformationChan, David. Breast Cancer: Real Questions, Real Answers. New York: Marlowe & Company, 2006. Firedewald, Vincent, M. D. Buzdar, and Michael Bokulich. Ask the Doctor: Breast Cancer. Kansas City, Mo.: Andrews McMeel, 1997. Link, John. Breast Cancer Survival Manual: A Step-by-Step Guide for the Woman with Newly Diagnosed Breast Cancer. 4th ed. New York: Holt, 2007. Other Resources American Cancer Society http://www.cancer.org Angiogenesis Foundation About Angiogenesis http://www.angio.org/understanding/understanding.html MayoClinic.com Angiogenesis Inhibitors: New Cancer Drugs Stop Tumor Growth http://www.mayoclinic.com/health/angiogenesis/CA00079 National Breast Cancer Foundation http://www.nationalbreastcancer.org See Also Angiogenesis inhibitors; biologic therapies; cancer biology; epidemiology of cancer; genetics of cancer; human growth factors and tumor growth; mutagenesis and cancer; protooncogenes and carcinogenesis. |
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