Definition

CD47 (cluster of differentiation 47, MER6, OA3), also known as integrin-associated protein (IAP), is a transmembrane protein encoded by the CD47 gene in humans. CD47 belongs to the immunoglobulin superfamily and binds to membrane integrin, as well as ligand platelet-reactive protein-1 (TSP-1) and signal regulatory protein α (SIRPα). CD-47 acts as a "don't eat me" signal to the immune system's macrophages, making it a potential therapeutic target for certain cancers and, more recently, to treat fibrosis in lung cancer.

CD47 is involved in a range of cellular processes, including apoptosis, proliferation, adhesion, and migration. In addition, it plays a key role in immune and angiogenic responses. CD47 is commonly expressed in human cells and has been found to be overexpressed in many different tumor cells. Expression in horse skin tumors has also been reported.

CD47 is a membrane receptor with an extracellular N-terminal IgV domain, five transmembrane domains, and a short C-terminal intracellular tail. CD47 has four variable splicing subtypes, which differ only in the length of its cytoplasmic tail. Type 2 is the most widely expressed form of all circulating and immune cells. The second most abundant isomer is type 4, which is mainly expressed in the brain and peripheral nervous system.

Fig. 1 Schematic Representation of The Structure of CD47

Function

Thrombospondin (TSP)

CD47 is a high-affinity receptor for platelet-reactive protein-1 (TSP-1), a secreted glycoprotein that plays a role in angiogenesis and angiogenesis, and in this later ability, TSP1-CD47 interactions inhibit multiple levels of nitric oxide signaling in vascular cells. The binding of TSP-1 to CD47 affects several essential cellular functions, including cell migration and adhesion, cell proliferation or apoptosis, and plays a role in the regulation of angiogenesis and inflammation.

Signal-regulatory Protein (SIRP)

CD47 interacts with the signal regulatory protein α (SIRPα), an inhibitory transmembrane receptor present on bone marrow cells. CD47/SIRPα interactions lead to bidirectional signaling, leading to different cell-to-cell responses, including inhibition of phagocytosis, stimulation of intercellular fusion, and T cell activation.

Integrins

CD47 interacts with a variety of membrane integrins, the most common being integrins αVβ3. These interactions generate CD47/ integrin complexes that affect a range of cellular functions, including adhesion, spreading, and migration.

Cancer cells use the "Don't eat me" mechanism to express high levels of CD47 on the surface of tumor cells to achieve immune escape. The researchers believe that inhibiting CD47 signaling in cancer cells may promote the phagocytosis of tumor cells by macrophages, thereby limiting tumor growth, which provides a new feasible immune target for anti-tumor therapy.

Fig. 2 The Regulatory Mechanism of CD47 eExpression

Clinical Application

CD47 was first identified as a tumor antigen in human ovarian cancer in the 1980s. Since then, CD47 has been found to be expressed in a variety of human tumor types, including acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), bladder cancer, and other solid tumors. Despite high levels of calreticulin (the main phagocytosis signal), high levels of CD47 allow cancer cells to avoid phagocytosis. This is due to CD47 binding to SIRP-α of macrophages. The involvement of SIRP-α results in inhibition of phagocytosis. Therefore, blocking CD47 with antibodies shuts down the "don't eat me" signal and favors phagocytosis. Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages elicits an antitumor T-cell immune response. Anti-cd47 antibody treatment not only enables macrophages to phagocytose cancer but also promotes the activation of tumor-specific lymphocytes.

Fig.3 Mechanism of Action of Targeting CD47-SIRP α

At present, there are four mechanisms of action of targeting CD47-SIRPα in tumor therapy:

1. Stimulate the phagocytosis of macrophages to cancer cells. CD47 antibodies, SIRPα antibodies, or recombinant SIRPα proteins inhibit the formation of CD47-SIRPα complexes, resulting in macrophages phagocytosis tumor cells.

2. Promote adaptive immune response. CD47 antibodies promote dendritic cells (DCs) to phagocytose tumor cells, which are subsequently presented to T cells (CD4+ and CD8+), stimulating an anti-tumor adaptive immune response.

3. Induce apoptosis of tumor cells. CD47 antibodies increase tumor cell clearance by inducing apoptosis through a caspase-independent mechanism.

4. Activate innate immune response. CD47 antibody eliminates tumor cells by NK cell-mediated antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

Alpha Lifetech Inc. is dedicated to developing CD47 diagnostic regents. Alpha Lifetech Inc. is a reputable supplier focusing on research, manufacture and sales of In Vitro Diagnostic (IVD) regents. All the IVD regents offered by Alpha Lifetech Inc. have undergone strict QC validation and are certified by the COA (certificate of analysis). Meanwhile, we can provide customized services according to customers' requirements. Alpha Lifetech Inc. is committed to supplying high-quality, high-sensitivity antigen and antibody products for scientific research and industrial customers. In addition to regular small packages, Alpha Lifetech Inc.'s large-scale fermentation platform also allows us to provide raw material-grade IVD regents for the majority of industrial customers.

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