CD146 is a protein found on the surface of various cells throughout the body. It plays a fundamental role in how cells interact and move within tissues, governing intricate communication and organization. Understanding CD146 provides insight into how our bodies maintain health and respond to disease.
What is CD146
CD146, also known as Melanoma Cell Adhesion Molecule (MCAM) or MUC18, is a protein located on the outer surface of cells. It is classified as a transmembrane glycoprotein, meaning it spans the cell membrane and has sugar molecules attached. This protein was initially identified in 1987 as a 113-kDa glycoprotein on human melanoma cells.
CD146 is primarily found on endothelial cells, which form the inner lining of blood vessels, and also on certain immune cells and some stem cells. Its structure includes five immunoglobulin-like domains, a part that crosses the cell membrane, and a short internal segment. This arrangement allows CD146 to function as a cell adhesion molecule, mediating interactions between cells and contributing to tissue integrity.
CD146’s Normal Biological Roles
CD146 plays a significant role in the formation of new blood vessels, a process known as angiogenesis. Its expression on endothelial cells and their precursors indicates its involvement in both healthy and disease-related vessel development. Blocking CD146 can reduce the formation of new vessels, affecting blood flow and vessel structure.
This protein also helps maintain the integrity of blood vessel walls, ensuring they remain cohesive and functional. It is predominantly expressed at the junctions between endothelial cells, where it contributes to the stability of the vascular lining. CD146 also influences the movement of immune cells through tissues, a process known as transendothelial migration.
CD146 is found on certain stem cells, such as mesenchymal stem cells, where it contributes to their development. It also plays a part in tissue repair processes. The presence of CD146 on these diverse cell types underscores its broad involvement in maintaining healthy physiological functions.
CD146 in Disease States
The levels or activity of CD146 can be altered in various pathological conditions, contributing to disease progression. In cancer, CD146 plays a significant role in the spread of malignancies. Its expression is often higher in metastatic lesions and advanced primary tumors compared to benign moles or early-stage melanomas.
CD146 contributes to tumor angiogenesis, the formation of new blood vessels that supply nutrients to growing tumors. It also facilitates metastasis, the process by which cancer cells spread from the original tumor to other parts of the body. Its presence allows melanoma cells to interact with components of the vascular system, promoting their spread through the bloodstream. CD146’s involvement extends beyond melanoma to other cancers, including prostate, breast, and ovarian cancers.
Beyond cancer, CD146 has implications in cardiovascular diseases. Its contribution to blood vessel dysfunction and inflammation can be seen in conditions like atherosclerosis, where arteries harden, and hypertension, characterized by high blood pressure. CD146 is expressed by components of the blood vessel wall, including endothelial cells and smooth muscle cells. Its modulation is a promising target for vascular disease therapy.
CD146 is also a factor in chronic inflammatory and autoimmune conditions, such as rheumatoid arthritis and multiple sclerosis. Its role in the movement of immune cells through vessel walls and its impact on endothelial permeability link it to the inflammatory response. For example, removing CD146 function in pulmonary endothelial cells has been associated with increased endothelial permeability and monocyte infiltration in a model of chronic obstructive pulmonary disease.
CD146 as a Diagnostic and Therapeutic Tool
The characteristics of CD146 make it a valuable target in medical diagnosis and treatment. Its potential as a diagnostic marker is explored for early detection and predicting outcomes in diseases like cancer and cardiovascular conditions. For instance, soluble CD146, a form of the protein found in the blood, can be measured to monitor disease progression. This soluble form is generated when the membrane-bound CD146 is shed from the cell surface.
CD146’s presence on specific cell types and its involvement in disease processes make it an attractive therapeutic target. Ways to target CD146 for new treatments, especially in cancer, are being investigated. Approaches include using antibodies to block CD146 function, which can inhibit tumor growth and metastasis. For example, fully human antibodies targeting MCAM/MUC18 have been shown to inhibit tumor growth and metastasis in human melanoma.
Drugs that specifically interact with CD146 to modulate its activity in various disease states are under development. The modulation of CD146 expression represents a promising avenue for therapies aimed at vascular diseases. These efforts highlight CD146’s potential to contribute to future diagnostic tools and novel treatment strategies.