The CD24 protein is a small, highly expressed molecule found on the surface of various cell types, where it functions as a key player in cellular communication. Its structure allows it to govern important biological processes, including the development of the immune system and the progression of cancer. The molecule is classified as a glycosylphosphatidylinositol (GPI)-anchored glycoprotein, a structural detail that dictates how it interacts with the cell membrane and transmits signals. This dual role in both normal physiology and serious disease has made CD24 a subject of intense scientific interest.
What is the CD24 Protein?
CD24 is a small, heavily glycosylated protein that is tethered to the outer leaflet of the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. The protein core is short, consisting of only about 31 to 35 amino acids in humans, but it is heavily modified by sugar molecules, giving it mucin-like characteristics. The GPI anchor allows the protein to reside within lipid rafts, specialized microdomains on the cell surface that serve as platforms for organizing signaling molecules.
This location enables CD24 to communicate with other cells, primarily by acting as an adhesion molecule and a ligand for other receptors. Historically, the protein was identified as a marker for blood cells, which is why it belongs to the Cluster of Differentiation (CD) nomenclature. Although the GPI anchor means CD24 lacks a direct connection to the cell’s interior, it can modulate signaling by associating with other transmembrane receptors and activating Src-family protein tyrosine kinases, such as Lyn and Fyn.
How CD24 Regulates the Immune System
CD24 plays a role in the immune system, regulating both development and inflammatory response. It is prominently expressed on cells of the innate and adaptive immune systems, particularly B lymphocytes, where its expression level changes significantly as the cell matures. In the bone marrow, CD24 is highly expressed on early B-cell progenitors and is involved in B-cell selection and differentiation. Engagement of CD24 at this stage can induce apoptosis, or programmed cell death, in developing B cells, which eliminates potentially harmful autoreactive cells.
In T cells, CD24 expression is transient, typically decreasing after maturation but rapidly increasing upon T-cell activation. The presence of CD24 on antigen-presenting cells, such as dendritic cells, is necessary for the optimal proliferation and expansion of T cells, demonstrating its involvement in initiating an effective immune response. The protein also helps modulate immune tolerance and prevents excessive inflammation. CD24 can suppress inflammatory responses by binding to danger-associated molecular patterns (DAMPs) released from damaged cells, helping the immune system distinguish between damage-induced signals and those caused by pathogens.
CD24’s Role in Cancer
The regulation CD24 performs in normal cells becomes corrupted in many malignancies, making it a significant factor in oncology. High CD24 expression has been observed in a wide variety of human cancers, including ovarian, breast, prostate, and colorectal cancers. Its presence often correlates with a poor clinical outcome and reduced survival rates. In a malignant context, CD24 often functions as a pro-survival and pro-metastatic molecule, promoting tumor progression.
A major mechanism of its malignancy-promoting function is its role as a marker for cancer stem cells (CSCs). CSCs are a small subpopulation of tumor cells believed to drive tumor initiation, recurrence, and resistance to standard treatments. Cells with a high expression of CD24 often exhibit enhanced tumor-initiating capacity and greater clonogenic ability. CD24 promotes tumor cell survival by contributing to anti-apoptotic effects, helping cancer cells evade programmed death signals.
CD24 facilitates metastasis, the spread of cancer, by acting as a ligand for P-selectin, an adhesion molecule found on activated platelets and endothelial cells. The binding of CD24-expressing tumor cells to P-selectin allows the cancer cells to attach to the inner lining of blood vessels, a crucial step for tumor cells to exit the bloodstream and colonize distant organs. This interaction with platelets also helps the tumor cells form clusters, protecting them from the shear stress of blood flow and immune surveillance, enhancing their metastatic fitness.
CD24’s function in immune evasion acts as a non-conventional immune checkpoint, often described as a “don’t eat me” signal. On the surface of cancer cells, CD24 binds to Siglec-10, an inhibitory receptor found on immune cells like macrophages and natural killer cells. This engagement suppresses the ability of macrophages to phagocytose the cancer cell, allowing the tumor to escape detection and destruction by the innate immune system.
Targeting CD24 in Diagnosis and Treatment
The association of CD24 with poor prognosis and its direct involvement in tumor survival and immune evasion has established it as a promising biomarker and therapeutic target. Clinically, measuring CD24 levels can be used as a prognostic biomarker in several cancer types, including ovarian, breast, and pancreatic cancers. High expression often indicates a more aggressive disease course and helps clinicians predict patient outcomes and resistance to certain therapies.
Current treatment strategies focus on blocking the detrimental functions of CD24 to re-engage the immune system against the tumor. Several therapeutic modalities are being explored:
- Monoclonal antibodies are designed to block the CD24/Siglec-10 interaction, turning off the “don’t eat me” signal and enhancing macrophage-mediated phagocytosis.
- Antibody-drug conjugates (ADCs) use the CD24 antibody as a homing device to deliver chemotherapy agents directly to CD24-expressing cancer cells.
- Chimeric Antigen Receptor (CAR) T-cell therapy is being adapted to target CD24, using engineered immune cells to specifically recognize and destroy tumor cells.
These approaches exploit the high and differential expression of CD24 on tumor cells compared to most healthy tissues.