CD24 - CD24 molecule |Elisa - Clia - Antibody - Protein

Background

CD24 is a small, heavily glycosylated cell surface protein that plays a crucial role in modulating immune responses, cell adhesion, and signal transduction. It is expressed in a wide range of tissues, including hematopoietic cells, neurons, epithelial cells, and cancer cells. CD24 has gained significant attention for its role in the immune system and its involvement in cancer biology. It has been implicated in both autoimmune diseases and tumor progression, making it an important molecule for understanding various pathophysiological processes.

CD24 is involved in modulating immune responses, particularly in the context of inflammation, tumor immunology, and autoimmunity. It acts as a key regulator of innate immunity by interacting with various receptors, such as Siglec-10 on macrophages, to dampen inflammatory responses and promote immune tolerance. In the tumor microenvironment, CD24 can contribute to the immune evasion of cancer cells, allowing them to escape destruction by the immune system.

In addition to its roles in immunity and cancer, CD24 is involved in neural development, cell migration, and adhesion, underlining its diverse biological functions. Its role in promoting cell adhesion and migration is particularly relevant in the context of metastasis, where CD24 expression is associated with enhanced metastatic potential of certain cancers.

Protein Structure

The CD24 molecule is a small, glycosylphosphatidylinositol (GPI)-anchored cell surface protein. Despite its modest size (around 30–60 amino acids, depending on species and post-translational modifications), CD24's extensive glycosylation contributes significantly to its molecular mass and functional diversity. The mature form of CD24 is synthesized as a pre-protein, which undergoes cleavage of the signal peptide and GPI-anchor addition.

Structural components of CD24 include:

Extracellular Domain:

• The extracellular portion of CD24 is relatively short but heavily modified with N-linked and O-linked glycans. These glycans play crucial roles in CD24's function, particularly in cell adhesion and immune modulation. The carbohydrate-rich nature of the extracellular domain is essential for its interactions with other cell surface receptors, such as Siglec-10 and P-selectin. CD24’s glycosylation patterns are known to vary in different cell types and conditions, which can affect its binding affinity and signaling potential.

GPI Anchor:

• CD24 is anchored to the cell membrane through a GPI anchor rather than a transmembrane domain. The GPI-anchor enables CD24 to be localized within lipid rafts, specialized microdomains in the plasma membrane that play a role in signal transduction. The GPI-anchor can also be cleaved, releasing soluble CD24 into the extracellular environment. This soluble form of CD24 can interact with immune cells and influence various signaling pathways.

Post-Translational Modifications:

• CD24 undergoes extensive post-translational modifications, particularly glycosylation, which is critical for its biological functions. These modifications help CD24 interact with glycan-binding receptors, regulate immune responses, and mediate cell adhesion processes. The glycosylation also contributes to CD24’s resistance to proteolytic cleavage, enhancing its stability and longevity on the cell surface.

Classification and Subtypes

CD24 belongs to the family of glycosylphosphatidylinositol (GPI)-anchored proteins, a group of proteins that are anchored to the cell membrane via a GPI moiety. CD24 is not known to have distinct subtypes in the traditional sense; however, its function and expression can vary significantly depending on the cell type and the disease context. For example, CD24 is differentially expressed in hematopoietic cells, neuronal tissues, and various cancers.

In immune cells, CD24 is primarily found on B cells, dendritic cells, and granulocytes, where it is involved in regulating the immune response. In contrast, CD24 expression in neural tissues plays a role in axon guidance and neuronal migration.

Function and Biological Significance

CD24’s primary roles are centered on its ability to modulate immune responses, facilitate cell adhesion, and contribute to tissue development, particularly in the nervous system. Key functions of CD24 include:

Immune Modulation:

• CD24 has emerged as a critical regulator of immune homeostasis and inflammation. It modulates both innate and adaptive immune responses, often serving as an inhibitory signal to prevent excessive inflammation. CD24 interacts with Siglec-10 (sialic acid-binding immunoglobulin-like lectin-10) on macrophages and dendritic cells, which leads to the suppression of inflammatory cytokine production and the induction of immune tolerance.
• This interaction is particularly important in autoimmunity, where CD24 helps to prevent self-reactive immune responses. CD24’s role in dampening inflammatory signals also helps control immune responses during infections and tissue damage, preventing chronic inflammation and tissue destruction.

Role in Tumor Immunology:

• CD24 is highly expressed in many tumor types, including breast cancer, colorectal cancer, and ovarian cancer. Its expression on tumor cells contributes to immune evasion by interacting with Siglec-10 on tumor-associated macrophages, promoting an anti-inflammatory, tumor-permissive environment. This allows cancer cells to avoid detection and destruction by the immune system.
• CD24 also facilitates tumor cell adhesion and migration, contributing to the metastatic spread of cancer cells. Increased expression of CD24 is often associated with a poor prognosis in several cancers, making it a potential target for immunotherapy.

B Cell Development:

• CD24 is expressed on early B cells in the bone marrow and plays a role in their development and maturation. It is downregulated as B cells mature and leave the bone marrow. CD24 is often used as a marker for early-stage B cells, especially in research and clinical settings, to identify progenitor B cells or immature B cells.

Neuronal Development:

• In the nervous system, CD24 is involved in neuronal migration and axon guidance. During central nervous system development, CD24 expression on neurons facilitates the correct navigation of axons and the formation of synaptic connections. The absence of CD24 can lead to defects in neuronal patterning and connectivity, underscoring its importance in neurodevelopment.

Clinical Issues

Cancer:

• CD24 is overexpressed in several types of cancers, including breast, pancreatic, lung, and ovarian cancers. Its expression is associated with increased tumor aggressiveness, enhanced metastatic potential, and poor patient outcomes. CD24-positive cancer cells are often more resistant to chemotherapy and immune system attack, making CD24 a potential target for cancer therapy.
• In the context of cancer immunotherapy, strategies aimed at blocking CD24-Siglec-10 interactions have been explored to enhance the immune system’s ability to recognize and destroy tumor cells. For example, anti-CD24 monoclonal antibodies are being investigated in clinical trials for their ability to disrupt the immune evasion mechanisms of tumors.

Autoimmune Diseases:

• Given its role in immune regulation, CD24 has been implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) and multiple sclerosis (MS). In these conditions, abnormal CD24 signaling may lead to improper immune tolerance, contributing to autoimmune attack against self-tissues. Therapeutic modulation of CD24 could potentially restore immune balance in these diseases by suppressing aberrant immune activation.

Infection and Inflammation:

• CD24 is involved in regulating the immune response to infections and tissue damage. Its interaction with Siglec-10 on immune cells helps control inflammation by limiting the production of pro-inflammatory cytokines. This is particularly relevant in conditions like sepsis, where excessive inflammation can lead to tissue damage and organ failure. Modulating CD24-Siglec signaling could be a therapeutic approach to reducing inflammatory damage in such cases.

Transplantation:

• CD24 has been explored as a marker for identifying immune cells that may contribute to graft rejection in organ transplantation. CD24-positive cells, particularly B cells, have been linked to graft-versus-host disease (GVHD) and other complications following transplantation. Monitoring and modulating CD24 expression in transplant recipients could help improve graft survival and reduce immune-mediated rejection.

Summary

CD24 is a small, GPI-anchored, heavily glycosylated protein that plays a significant role in immune modulation, tumor biology, neuronal development, and cell adhesion. It is expressed on a wide variety of cell types, including B cells, neurons, epithelial cells, and tumor cells. The extracellular domain of CD24 is characterized by extensive glycosylation, allowing it to interact with key immune regulatory molecules such as Siglec-10.

Clinically, CD24 is implicated in cancer progression, where its overexpression contributes to tumor immune evasion and metastasis, as well as in autoimmune diseases, where it helps regulate immune tolerance. The modulation of CD24-Siglec interactions presents a promising therapeutic strategy for both cancer treatment and autoimmune regulation. Additionally, CD24’s involvement in inflammatory processes and B cell development highlights its importance in immune system homeostasis.

Therapeutic approaches targeting CD24 are currently being explored, particularly in the context of cancer immunotherapy and autoimmune disease treatment.