AGR2 Specific Neutra™ Antibody Products

Anterior gradient protein 2 homolog (AGR2) is a protein of the protein disulfide isomerase (PDI) family, primarily localized in the endoplasmic reticulum. It contains endoplasmic reticulum localization and thioredoxin-like domains essential for its function in protein folding and chaperone activity. AGR2 is widely expressed in various tissues, with notable levels in the gastrointestinal tract, respiratory system, and certain cancers. AGR2 plays a role in protein folding, cell signaling, and promoting cellular proliferation and migration. Its dysregulation has been linked to cancer development, making it a potential target for cancer diagnosis and therapy. AGR2 is a potential anti-tumor target and anti-AGR2 neutralizing antibodies are promising anti-tumor drug candidates by blocking the AGR2 functions.

Its Gene ID: 10551, UniProtKB ID: O95994, and OMIM ID: 606358.

Fig.1 AGR2 protein architecture.¹

Interaction Partners and Regulation of AGR2

Intracellular and extracellular AGR2 can interact with a variety of proteins through their intrinsic motifs and secretion functions. Its interaction partners vary depending on the context but often include proteins like ERp57, EGFR and MUC2. These interactions can influence AGR2's function in promoting cell proliferation, migration, and invasion. Its expression is regulated by factors like ER stress, estrogen, and inflammatory cytokines, highlighting its role in cell homeostasis and disease pathways.

The Role of AGR2 in Cancer

The evidence that AGR2 may be involved in tumor biology arises from several studies primarily concerning hormone-dependent tumors such as breast, prostate and ovarian cancers, and non-hormone cancers such as neoplasia of the gastro-intestinal tract and lungs. AGR2 promotes cancer development by influencing cell proliferation, survival, and invasion, as well as by modulating the tumor microenvironment. Additionally, it can interact with other proteins to regulate signaling pathways involved in cancer pathogenesis. For instance, the prometastatic characteristics of AGR2 are demonstrated by its interaction with two proteins participating in metastasis formation. Induction of AGR2 silencing results in reduced proliferation of pancreatic cancer cells.

Fig.2 The roles of AGR2 in sorafenib-sensitive and sorafenib-resistant hepatocellular carcinoma.²

AGR2 as a Therapeutic Target

AGR2 has emerged as a promising therapeutic target for cancer therapy, and treatment strategies targeting AGR2 have thus far shown encouraging outcomes.

• Anti-AGR2 monoclonal antibodies

The anti-AGR2 monoclonal antibodies can specifically bind to AGR2, inhibiting its oncogenic functions and prompting immune-mediated destruction of cancer cells. A mouse monoclonal antibody that was first developed against AGR2 has been proven to inhibit the growth of breast cancer cells in vitro, as well as increase survival and prevent AGR2-induced tumor progression in a preclinical animal model of lung cancer via regulating the p53 and MAPK pathways.

• AGR2-based bispecific antibodies

Bispecific antibodies targeting AGR2 and other molecules provide enhanced specificity and efficacy in cancer treatment, offering novel therapeutic approaches for combating AGR2-related malignancies. Bispecific antibodies constructed by AGR2 antibodies and PD-1protein have the potential to both target the tumor microenvironment and guide PD-1 inhibitors to enrich in the tumor bodies, and have been proven to show stronger anti-tumor response than the group of monotherapies.

Creative Biolabs offers high-quality anti-AGR2 monoclonal antibody products that could be used in several kinds of applications to assist you in effectively completing your research projects.

REFERENCES

1. Moidu, Nurshahirah Ashikin, et al. "Secretion of pro-oncogenic AGR2 protein in cancer." Heliyon 6.9 (2020).
2. Tsai, Hung-Wen, et al. "Anterior gradient 2 induces resistance to sorafenib via endoplasmic reticulum stress regulation in hepatocellular carcinoma." Cancer Cell International 23.1 (2023): 42.