The therapeutic potential of cartilage has been investigated for more than 30 years. As noted previously (refer to the General Information section of this summary for more information), cartilage products have been tested as treatments for people with cancer, psoriasis, and arthritis. Cartilage products have also been studied as enhancers of wound repair and as treatments for people with osteoporosis, ulcerative colitis, regional enteritis, acne, scleroderma, hemorrhoids, severe anal itching, and the dermatitis caused by poison oak and poison ivy. Reviewed in [2-5]
Early studies of cartilage’s therapeutic potential utilized extracts of bovine (cow) cartilage. The ability of these extracts to suppress inflammation was first described in the early 1960s. The first report that bovine cartilage contains at least one angiogenesis inhibitor was published in the mid-1970s. The use of bovine cartilage extracts to treat patients with cancer and the ability of these extracts to kill cancer cells directly and to stimulate animal immune systems were first described in the mid- to late-1980s.[7-10]
The first report that shark cartilage contains at least one angiogenesis inhibitor was published in the early 1980s, and the only published report to date of a clinical trial of shark cartilage as a treatment for people with cancer appeared in the late 1990s. The more recent interest in shark cartilage is due, in part, to the greater abundance of cartilage in this animal and its apparently higher level of antiangiogenic activity. Approximately 6% of the body weight of a shark is composed of cartilage, compared with less than 1% of the body weight of a cow. Reviewed in  In addition, on a weight-for-weight basis, shark cartilage contains approximately 1,000 times more antiangiogenic activity than bovine cartilage. Reviewed in 
As indicated previously (refer to the Overview and General Information sections of this summary for more information), at least three different mechanisms of action have been proposed to explain the anticancer potential of cartilage: 1) it is toxic to cancer cells; 2) it stimulates the immune system; and 3) it inhibits angiogenesis. Only limited evidence is available to support the first two mechanisms of action; however, the evidence in favor of the third mechanism is more substantial (refer to the Laboratory/Animal/Preclinical Studies section of this summary for more information).
The process of angiogenesis requires at least four coordinated steps, each of which may be a target for inhibition. First, tumors must communicate with the endothelial cells that line the inside of nearby blood vessels. This communication takes place, in part, through the secretion of angiogenesis factors such as vascular endothelial growth factor. Reviewed in [15-19] Second, the activated endothelial cells must divide to produce new endothelial cells, which will be used to make the new blood vessels. Reviewed in [16,18-21] Third, the dividing endothelial cells must migrate toward the tumor. Reviewed in [16-21] To accomplish this, they must produce enzymes called matrix metalloproteinases, which will help them carve a pathway through the tissue elements that separate them from the tumor. Reviewed in [19-23] Fourth, the new endothelial cells must form the hollow tubes that will become the new blood vessels. Reviewed in [18,19] Some angiogenesis inhibitors may be able to block more than one step in this process.
Cartilage is relatively resistant to invasion by tumor cells, Reviewed in [24-31] and tumor cells use matrix metalloproteinases when they migrate during the process of metastasis. Reviewed in [14,22,26,32,33] Therefore, if the angiogenesis inhibitors in cartilage are also inhibitors of matrix metalloproteinases, then the same molecules may be able to block both angiogenesis and metastasis. Shark tissues other than cartilage have also been reported to produce antitumor substances.[34-36] Reviewed in References
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