Cadherin 11 is a protein that governs how cells connect and interact. It belongs to the cadherin family of proteins, which are fundamental to the body’s structure and function. This particular cadherin is involved in normal physiological processes and the development of several diseases, making it a subject of scientific interest.
Understanding Cadherin 11: Structure and Location
Cadherin 11, encoded by the CDH11 gene, is a type II classical cadherin that mediates calcium-dependent cell attachment. As a transmembrane protein, it passes through the cell membrane. It has an extracellular portion with five distinct domains that binds with other cells, a segment anchored within the membrane, and an intracellular domain that connects to the cell’s internal cytoskeleton.
This structure allows it to act as both a physical linker and a communication conduit between cells. Cadherin 11 is found in specific cell types, with prominent expression in the fibroblast-like synoviocytes lining our joints and in osteoblasts, the cells responsible for building new bone.
During embryonic development, cadherin 11 is involved in forming various tissues and is also expressed in smooth muscle cells and certain cells in the brain and heart. In disease states, its presence can be noted in places where it is not normally found, such as on the surface of some types of cancer cells.
The Functional Importance of Cadherin 11
The primary function of cadherin 11 is mediating cell-to-cell adhesion. It accomplishes this through homophilic binding, where a cadherin 11 molecule on one cell binds to another on an adjacent cell. This “like-to-like” interaction ensures that similar cells stick together to form organized tissues.
These interactions guide tissue morphogenesis, the shaping of organs during embryonic development. By controlling how cells adhere and sort, cadherin 11 directs the formation of structures like the synovial lining in joints. The protein also influences cell migration, the coordinated movement of cells necessary for tissue repair and development.
Cadherin 11 also influences intracellular signaling pathways. When its molecules on neighboring cells bind, it triggers internal signals that affect cellular behavior. These signals regulate processes such as cell proliferation and differentiation, ensuring that cells divide when needed and mature into their specialized forms to maintain tissue integrity and function.
Cadherin 11 in Disease Pathogenesis
The dysregulation of cadherin 11 is implicated in several diseases, including inflammatory conditions like rheumatoid arthritis (RA). In RA, the protein is highly expressed on fibroblast-like synoviocytes in the joint lining. This promotes their aggregation into an invasive tissue called pannus, which attacks cartilage by stimulating the release of inflammatory molecules and destructive enzymes.
Cadherin 11 also has a role in cancer. In aggressive breast and prostate cancers, tumor cells can switch on its expression, allowing them to adhere to one another and invade surrounding tissue. This expression is also linked to metastasis, the process where cancer cells spread to distant organs, such as from the breast to bone.
Fibrotic diseases, involving excessive scar tissue formation, are also linked to cadherin 11. In conditions like idiopathic pulmonary fibrosis, its expression is elevated in fibroblasts. It promotes their transformation into myofibroblasts, which deposit large amounts of matrix, leading to tissue stiffening and organ dysfunction.
Therapeutic Opportunities Targeting Cadherin 11
Given its role in driving disease, cadherin 11 is a target for new medical treatments. The goal is to block the protein’s function, thereby disrupting the pathological processes in arthritis, cancer, and fibrosis. The primary focus is developing agents that inhibit its adhesive functions.
One approach involves creating monoclonal antibodies, which are lab-engineered proteins that bind to cadherin 11’s extracellular domain. This binding physically prevents it from linking cells together. Preclinical studies in animal models of rheumatoid arthritis and pulmonary fibrosis showed reduced joint inflammation and tissue scarring, and a monoclonal antibody has entered early-phase clinical trials for RA.
Another approach is developing small molecule inhibitors, which are chemical compounds that interfere with cadherin 11’s function. Research has explored repurposing existing drugs, like celecoxib, which can bind to the protein. The development of novel, highly selective small molecules is an ongoing effort to create convenient oral medications. These strategies represent an evolving field of biomedical research.