CD138, also known as Syndecan-1, is a protein found on the surface of various cells throughout the body. Proteins like this serve as molecular identifiers, helping clinicians distinguish different cell types and track their behavior. They are deeply involved in cellular communication, receiving external signals and transmitting them internally to direct cell activity. The presence, absence, or quantity of specific surface markers provides insights routinely used in the diagnosis and monitoring of numerous diseases.
Biological Identity and Structure
CD138 is formally identified as Syndecan-1 (SDC1), belonging to the syndecan family of transmembrane proteoglycans. Anchored to the cell membrane, the protein is composed of three distinct parts: a large extracellular domain, a transmembrane domain, and a short intracellular domain. The extracellular domain is typically decorated with long, negatively charged sugar chains (heparan sulfate and chondroitin sulfate glycosaminoglycans), classifying it as a heparan sulfate proteoglycan. These sugar chains are the primary binding sites, allowing CD138 to bind various external molecules. While expressed on many epithelial cells, CD138 is most highly expressed on terminally differentiated B-cells, known as plasma cells.
Roles in Healthy Cell Function
In non-diseased tissue, Syndecan-1 plays a role in maintaining tissue architecture and mediating cellular communication. Its presence is concentrated on the basal surface of epithelial cells, where it acts as a stabilizing element. This positioning helps maintain the integrity of the epithelial layer by linking the cell to the underlying extracellular matrix (ECM).
The heparan sulfate chains allow CD138 to bind to a wide array of ligands, including growth factors, chemokines, and ECM components like collagen. By binding these factors, CD138 helps regulate their availability and presentation to other cell surface receptors, influencing cell proliferation and migration. This modulation of signaling pathways is central to its involvement in processes like wound healing and tissue maintenance.
Primary Clinical Significance in Hematology
The highest clinical relevance of CD138 lies in its consistent and high expression on mature plasma cells, making it a definitive marker for diagnosing plasma cell disorders. It is widely considered the gold-standard surface marker for identifying malignant cells in Multiple Myeloma (MM), a cancer of the plasma cells. Pathologists use techniques like immunohistochemistry on bone marrow biopsies to visualize CD138 staining, confirming the presence and quantity of plasma cells.
In a clinical laboratory, CD138 expression is often assessed using multiparameter flow cytometry, frequently in combination with other markers like CD38. This method allows for the rapid identification and enumeration of plasma cells in bone marrow samples. The presence of a large, clonal population of CD138-positive cells helps confirm the diagnosis of MM.
However, the reliability of CD138 as a marker is complex, particularly in monitoring disease progression or treatment response. Studies show that some aggressive, drug-resistant myeloma cells can lose or downregulate CD138 expression, especially following certain therapies or during relapse. This emergence of a CD138-negative population is often associated with a poorer prognosis and resistance to chemotherapy.
The protein’s dynamic expression also impacts the assessment of minimal residual disease (MRD), where a small number of cancer cells remain after treatment. Because CD138 can be lost or diminished on residual cells, current diagnostic strategies rely on broader panels of markers to ensure all malignant clones are detected. Furthermore, CD138 can be cleaved from the cell surface and released into the bloodstream, where this soluble form can be measured as an indicator of disease activity and prognosis.
Involvement in Non-Hematological Pathologies
Beyond its role in blood cancers, the expression pattern of Syndecan-1 is altered in a wide variety of solid tumors and inflammatory conditions. In many epithelial cancers, the expression of CD138 is variable and can have opposite implications depending on the tumor type. For instance, in carcinomas of the breast, colon, and prostate, changes in CD138 expression are linked to the tumor’s behavior.
In several solid tumors, the loss of CD138 expression on the cell surface is associated with a process called epithelial-mesenchymal transition (EMT), which promotes metastasis and invasiveness. When epithelial cells lose their structural integrity to become migratory, they often shed CD138, allowing them to break away from the primary tumor mass. Conversely, in other contexts, high CD138 expression on tumor cells or the surrounding stroma can correlate with a poor outcome.
The shedding of CD138 from the cell surface also serves as a general indicator of tissue damage, particularly in inflammation. As a cell adhesion molecule, its cleavage releases the extracellular domain into the surrounding tissue or circulation. Elevated levels of soluble CD138 in the blood are observed in various inflammatory states, reflecting the degradation of cell-matrix attachments and general tissue disruption.