CD56 is a protein marker found on the surface of various cells, acting as a key identifier for scientists and doctors examining cell populations. This molecule is officially known as the Neural Cell Adhesion Molecule (NCAM), highlighting its foundational role in the nervous system. Detecting the presence, absence, and concentration of CD56 allows researchers to classify cell types and gain insight into normal biological processes and disease states. Its study bridges neurobiology and immunology, offering insights into cell-to-cell communication and immune regulation.
What CD56 Is and How It Functions
CD56 is a glycoprotein, meaning it is a protein with attached sugar chains, and it belongs to the immunoglobulin superfamily. Its primary function is as a Cell Adhesion Molecule (CAM), facilitating physical interaction between cells or between a cell and its surrounding matrix. This adhesive property occurs through homophilic binding, where the CD56 molecule on one cell binds to another CD56 molecule on a neighboring cell.
The molecule is encoded by the single gene NCAM1. Alternative splicing produces several isoforms, such as NCAM-120, NCAM-140, and NCAM-180, named based on their molecular weights. These different versions affect how the protein is anchored to the cell membrane and influence its signaling capabilities. In the nervous system, where it was first discovered, CD56 is important for processes like neurogenesis, nerve fiber extension (neurite outgrowth), and synapse formation. It helps structure nerve tissue by promoting cell-to-cell connections during development.
CD56’s Role in Immune Surveillance
CD56 is widely known as the defining surface marker for Natural Killer (NK) cells, a type of white blood cell. NK cells are part of the innate immune system and are responsible for the early defense against virus-infected and tumor cells. The NK cell population is divided into two major functional subsets based on the intensity of CD56 expression.
CD56-Bright Population
The CD56-bright population constitutes a minority of NK cells in the circulating blood, typically around 10%. These cells are generally found in higher concentrations in lymphoid tissues, such as lymph nodes, and at sites of inflammation. CD56-bright NK cells are primarily potent cytokine producers, releasing chemical messengers like interferon-gamma to regulate and coordinate the broader immune response. They are considered less mature and are only weakly cytotoxic before receiving activation signals.
CD56-Dim Population
The second, more abundant subset in peripheral blood is the CD56-dim population, making up about 90% of circulating NK cells. These cells are highly cytotoxic and possess a greater concentration of lytic granules containing molecules like perforin and granzymes. Their main function is the direct killing of abnormal cells, a process facilitated by the presence of the surface marker CD16. CD56-bright cells may represent a precursor population that can differentiate into the more mature, highly cytotoxic CD56-dim cells. CD56 expression is also found on a subset of T lymphocytes, where its presence correlates with a potent, NK-like cytotoxic function.
When CD56 Levels Signal Disease
The presence and level of CD56 expression are regularly used in clinical settings as a diagnostic marker to identify and classify various diseases, particularly cancers. Its detection is a powerful tool for distinguishing certain types of tumors from one another. In hematologic malignancies, such as cancers of the blood and lymph system, CD56 expression is considered an aberrant marker on malignant cells in conditions like plasma cell myeloma and some NK/T-cell lymphomas.
CD56’s association with the nervous system makes it a sensitive marker for tumors that arise from or show characteristics of neuroendocrine or neuroectodermal cells. For example, CD56 is expressed in over 85% of small cell carcinomas, including small cell lung cancer, making it a reliable diagnostic marker for this aggressive disease. It is also a common marker for Merkel cell carcinoma, a rare but aggressive skin cancer with neuroendocrine features.
Its high expression rate in small cell carcinoma is often greater than other traditional neuroendocrine markers. When CD56 is detected by flow cytometry on a non-leukocyte cell population (CD56+/CD45-), it serves as a rapid and specific indicator for the presence of a neuroendocrine malignancy. The loss of CD56 expression in certain tumors, such as pancreatic neuroendocrine neoplasms, signals a more aggressive tumor grade and an increased likelihood of organ invasion.