SEMA4A Specific Neutra™ Antibody Products

Semaphorin 4A (SEMA4A) is a 761 aa protein of the Semaphorin family, members of which are secreted in the nervous system and are originally identified as axon guidance factors. They are involved with the development of organs and systems such as kidneys, heart, and immune system. SEMA4A is a membrane-bound protein generally expressed by endothelial cells, but its extracellular portion can be processed into soluble form by proteolytic cleavage.

Its Gene ID: 64218, UniProtKB ID: Q9H3S1, and OMIM ID: 607292.

SEMA4A Functions and Signaling Pathways

SEMA4A is widely distributed in antigen-presenting cells (APC), such as T cells, dendritic cells (DCs), and macrophages, and it plays various roles in immune responses and many types of inflammatory disorders. There are four types of SEMA4A receptors, including the Plexin B family, the Plexin D family, Nrp-1, and Tim-2, among which Plexin-D1 serves as the functional receptor of SEMA4A on endothelial cells. Besides, SEMA4A binds to NRP-1 to upregulate the activation of T cells in inflammation. SEMA4A is essential in many biological processes, such as immune-cell activation, cell-cell interactions, cell differentiation, and cell migration. It is also reported that SEMA4A is involved in retinal systems and carcinogenesis.

SEMA4A is also revealed to be associated with cancers. In prostate cancer, SEMA4A is overexpressed in prostate cancer tissues, and directly regulated by STAT, inducing epithelial-mesenchymal transition of prostate cancer cells, thus promoting invasion by creating a positive loop in stromal cells with IL-10.

Fig.1 SEMA4A is directly regulated by STAT3.^{1, 3}

In lung cancer, SEMA4A promotes phosphorylation of NF-κB, MAPK, and STAT3 via enhancing PlexinB1 mRNA expression, thus elevating IL-6 production by up-regulating the NF-κB pathway. Since IL-6 is an important cytokine that upregulates the proliferation and migration of lung cancer cells, SEMA4A contributes to tumor development. The mechanism underlines the potential of SEMA4A to be a potential target for lung cancer treatment.

Fig.2 The mechanism model diagram of SEMA4A promotes lung cancer development.^{2, 3}

Antibodies Targeting SEMA4A

The diversity of roles and functions of SEMA4A in immune response and diseases highlight its potential as a promising target for research or clinical purposes. Antibodies targeting SEMA4A are being utilized as robust tools in investigations on the detailed mechanism of cancers and autoimmune diseases, and as therapeutic strategies in preclinical studies. In mice, an anti-SEMA4A antibody is reported to antagonize arsenic-induced hepatotoxicity, and inhibit AKT2/NF-κB inflammatory signaling, exhibiting a remarkable effect on histopathological features. In another study, it is demonstrated that targeting SEMA4A with antibody-drug conjugate selectively and significantly eliminates myeloma cells both in vitro and in vivo. These encouraging results suggest the feasibility of regarding SEMA4A as a therapeutic target for drug development.

Creative Biolabs offers different anti-SEMA4A antibody products. These antibodies are recombinantly expressed and could be used for various purposes. Customization of SEMA4A-based bispecific antibodies is also available for you here.

REFERENCES

1. Liu, Xiao, et al. "SEMA4A promotes prostate cancer invasion: involvement of tumor microenvironment." Journal of Cancer 14.14 (2023): 2633.
2. Wei, Xiang, et al. "Semaphorin4A promotes lung cancer by activation of NF-κB pathway mediated by PlexinB1." PeerJ 11 (2023): e16292.
3. Under open access license CC BY 4.0, without modification.