Research topic
Atherosclerosis, Bone and cartilage metabolism, Cardiovascular disease, Extracellular matrix, Pulmonary diseases
Summary
Cartilage oligomeric matrix protein (COMP), also designated thrombospondin 5 (TSP 5), is a non-collagenous glycoprotein and is a member of the thrombospondin family of extracellular proteins. COMP is a calcium-binding protein of high molecular weight (>500kDa) present in the extracellular matrix of articular, nasal and tracheal cartilage. COMP is not only cartilage-derived but was found widely in other tissues, including synovium and tendon. Intact COMP is pentameric, with five identical subunits and the carboxy-terminal globular domain of native COMP binds to collagens I, II, and IX. It has been proposed that COMP molecules are important for maintaining the properties and integrity of collagen network. In addition COMP may have a storage and delivery function for hydrophobic cell-signaling molecules such as vitamin D.
The significance of COMP for normal development and function of cartilage has been underscored by the discovery that mutations of the COMP gene result in pseudoachondro¬plasia and some forms of multiple epiphyseal dysplasia. Most published studies have shown that serum levels of COMP provide important information about metabolic changes occurring in the cartilage matrix in joint disease. These studies describe that serum COMP level correlated with cartilage degradation and is a potential prognostic marker in inflammatory joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). Results have demonstrated an association of increasing serum COMP levels with progressive destruction of articular cartilage monitored radiographically. OA and RA are common diseases causing pain and disability in a significant proportion of the adult population and early diagnostics of these diseases is very important for future therapy.
COMP, abundant in cartilage, is now known to be also expressed in tumor tissues from breast, prostate, and colon cancer. Studies have concluded that COMP in breast cancer cells is correlated with poor survival and higher recurrence rates in patients. Elevated levels of COMP in sera can be detected in metastatic breast cancer patients compared with those in early stages of the disease. Additionally, serum COMP could potentially be an independent prognostic marker for metastatic patients. Similarly, studies have shown that COMP expression in prostate cancer correlated with enhanced invasion and with a more progressive disease. Likewise, COMP expression has been correlated with the poor outcome of colon cancer patients. COMP levels in the sera of preoperative patients with colon cancer were much higher than those in healthy donors and were significantly reduced after colectomy. Thus, COMP may be a novel prognostic indicator and biomarker and also a potential therapeutic target for colon cancer.
Increased COMP has been associated with fibrogenesis in systemic sclerosis, skin keloids, vascular atherosclerosis, lung fibrosis, and chronic pancreatitis. Studies have also suggested that COMP contributes to liver fibrosis by regulating collagen-I deposition, with further investigation finding that serum COMP levels could be used as a non-invasive liver fibrosis marker in patients with chronic viral hepatitis (CVH). There is evidence that COMP plays a role in pathogenesis of idiopathic pulmonary fibrosis (IPF) and should be further evaluated as a biomarker for disease activity in IPF.
There is evidence that COMP is essential for maintaining vascular homeostasis, and is an endogenous thrombin inhibitor and negative regulator of hemostasis and thrombosis. Research suggests a pathogenetic role of COMP the development of vascular fibrosis and calcification, and thus COMP may be a novel target in therapy of a number of vascular diseases.
