CD90, also known as Thy-1, is a complex protein found on the surface of various cells throughout the body. This protein plays diverse roles in how cells interact with each other, how nerves regenerate, and how different cancers develop.
Understanding CD90
CD90 is a small membrane glycophosphatidylinositol (GPI)-anchored protein, typically ranging from 25 to 37 kilodaltons (kDa). It is heavily N-glycosylated, meaning it has many sugar chains attached to it, which can account for roughly one-third of its total mass. The protein consists of a single V-like immunoglobulin domain, which is a structural motif also found in antibodies. This domain is anchored to the cell’s outer membrane by a GPI linkage.
Despite lacking an intracellular domain, CD90 is capable of transmitting signals inside cells. It resides within specialized areas of the cell membrane called lipid rafts, which are rich in lipids and cholesterol. Within these rafts, CD90 can interact with other proteins, such as G inhibitory proteins, Src family kinases like Src and c-Fyn, and tubulin, allowing it to influence cellular processes. This signaling capacity enables CD90 to participate in various cellular activities, even without a direct cytoplasmic tail.
Where CD90 is Found
CD90 exhibits diverse expression patterns across different cell types and tissues, with its presence varying between species. In humans, CD90 is found on neurons, particularly in mature axons, and its levels increase during postnatal brain development. It is also present on hematopoietic stem cells (HSCs), which are cells that can develop into all types of blood cells.
CD90 is also expressed on endothelial cells, which line blood vessels, and smooth muscle cells. Some fibroblasts, which are cells that contribute to connective tissue, also express CD90. The protein is considered a significant marker for various types of stem cells, including mesenchymal stem cells and hepatic stem cells, indicating its role in identifying these undifferentiated cell populations.
How CD90 Functions
CD90 participates in a range of biological functions, often involving interactions at the cell surface. It plays a role in cell-cell and cell-matrix interactions, influencing how cells adhere to each other and to their surrounding environment. The protein is known to interact with integrins, which are cell surface receptors that mediate cell adhesion and signaling, often through an Arg-Gly-Asp (RGD)-like motif. These interactions are involved in regulating cell adhesion, extravasation (the movement of cells from blood vessels into tissues), and cell migration.
CD90 also contributes to nerve regeneration and axon growth, processes that are important for nervous system repair. Beyond these roles, CD90 is involved in modulating fibrosis, a process of tissue scarring, and has implications in inflammation and apoptosis (programmed cell death). For instance, in lung fibroblasts, CD90 can promote apoptosis and inhibit their differentiation into myofibroblasts, which are cells that contribute to fibrosis.
CD90 in Health and Disease
CD90’s role in health and disease is complex, often exhibiting contradictory effects depending on the specific context. In cancer, CD90 can act as either a promoter or a suppressor of tumor growth. It has been identified as a candidate marker for cancer stem cells (CSCs) in several malignancies, including high-grade gliomas, liver cancer, gastric cancers, and esophageal squamous cell carcinomas.
High CD90 expression in glioblastoma (GBM) patients is associated with invasive characteristics and can predict patient response to certain therapies. CD90-positive lung cancer cells have shown higher proliferative and tumorigenic capacities. Conversely, in other cancers, CD90 can function as a tumor suppressor. For example, in ovarian adenocarcinoma, decreased CD90 expression is linked to a poorer prognosis, and its presence can inhibit tumor formation and reduce stemness. Similarly, in nasopharyngeal carcinoma, CD90 acts as a tumor suppressor by maintaining cell-cell adhesion and inhibiting certain signaling pathways, suppressing tumor invasion and metastasis.