CD166, also known as Activated Leukocyte Cell Adhesion Molecule (ALCAM), is a type I transmembrane glycoprotein found on the surface of various cell types throughout the human body. It is embedded within the cell membrane, allowing it to interact with the extracellular environment and other cells. This protein belongs to the immunoglobulin superfamily. Its presence facilitates diverse cell-to-cell interactions, playing a foundational role in how cells communicate and organize within tissues.
Fundamental Functions of CD166
CD166 operates as a cell adhesion molecule, mediating both homophilic and heterophilic interactions. Homophilic binding occurs when CD166 on one cell binds to CD166 on an adjacent cell, contributing to cell clustering and tissue integrity. Heterophilic interactions involve CD166 binding to other molecules, such as CD6 on activated leukocytes, influencing immune responses and T-cell development.
Beyond its direct adhesive roles, CD166 is involved in cell migration, a process where cells move from one location to another, necessary for development and repair. Its interactions can influence cellular behavior by initiating various signaling pathways within the cell. For instance, CD166 has been linked to the regulation of Wnt signaling, a pathway involved in cell proliferation and differentiation. Through its association with scaffolding proteins, CD166 can also connect to the actin cytoskeleton, linking it to intracellular signaling networks that govern cell adhesion and movement.
CD166 in Tissue Development and Regeneration
CD166 on various stem cell populations highlights its involvement in tissue formation and repair. It is expressed on mesenchymal stem cells, which are multipotent cells capable of differentiating into various cell types, and on hematopoietic stem cells, which give rise to all blood cell types. In the bone marrow, CD166 is necessary for the proper engraftment of hematopoietic stem cells.
CD166 also contributes to the organization and function of specific tissue networks. It is required for the normal formation of lymph vessel networks and plays a part in neurogenesis, the process of forming new neurons. The protein promotes neurite extension, axon growth, and axon guidance, which contribute to nervous system development and function. In intestinal tissues, CD166 helps regulate the balance between stem cell proliferation and differentiation, maintaining epithelial homeostasis.
CD166 in Disease Progression
Alterations in CD166 expression levels are frequently observed in various disease states, particularly in cancer. Its expression can be higher in certain types of tumors, where it contributes to tumor growth, invasion, and the spread of cancer cells to distant sites, known as metastasis. For example, in melanoma, increased CD166 expression may indicate a more aggressive, invasive phenotype.
In colon cancer, CD166 aids in the adhesion of cancer cells to the extracellular matrix. In ovarian cancer, CD166 promotes cancer stem-like properties, including increased proliferation, migration, adhesion, and resistance to certain drugs. It has also been identified on glioblastoma progenitor cells, suggesting its involvement in tumor invasion.
Beyond cancer, CD166’s role in cell adhesion and migration also implicates it in inflammatory conditions. In rheumatoid arthritis, where immune cells attack joints, CD166 is involved in the activation and movement of these immune cells. CD166 is being explored as a potential diagnostic marker and as a therapeutic target. Inhibitors designed to interfere with CD166’s interactions are being investigated as strategies to modulate its activity and potentially treat diseases like cancer and inflammatory disorders.