Anterior Gradient 2 (AGR2) is a 20 kDa protein belonging to the protein disulfide isomerase (PDI) family, primarily localized in the endoplasmic reticulum (ER). It plays a critical role in protein folding and quality control by catalyzing disulfide bond formation, particularly in secretory and transmembrane proteins. AGR2 also functions as a secreted protein under certain conditions, influencing extracellular signaling pathways involved in cell proliferation, adhesion, and metastasis. Its expression is tightly regulated under physiological conditions but is frequently dysregulated in diseases, notably cancer. Overexpression of AGR2 has been observed in various malignancies, including breast, prostate, and gastrointestinal cancers, where it promotes tumor growth, chemoresistance, and metastatic spread by modulating ER stress responses, EMT (epithelial-mesenchymal transition), and interactions with oncogenic pathways like EGFR and HER2. Conversely, AGR2 downregulation is linked to inflammatory bowel diseases (IBD), suggesting tissue-specific roles.
AGR2-specific antibodies are essential tools for detecting its expression and localization in research and diagnostics. These antibodies, often generated using recombinant AGR2 protein or peptide fragments, enable techniques such as immunohistochemistry (IHC), Western blotting, and ELISA. They help identify AGR2 as a potential biomarker for cancer prognosis or therapeutic targeting. However, challenges remain in ensuring antibody specificity due to structural similarities within the PDI family. Recent advances in monoclonal antibody development have improved selectivity, aiding in distinguishing AGR2 from homologs like AGR3. Studies also explore neutralizing antibodies to block AGR2's extracellular oncogenic signaling, highlighting its dual role as both an intracellular chaperone and extracellular ligand.