GPC3 Antibodies

Structure of GPC3

GPC3 is a cell membrane protein with a relatively large molecular weight, and the molecular weight of its core protein is approximately 70 kDa. Due to the extensive glycosylation modification of this protein after translation, the actual molecular weight of its glycosylation form shows significant heterogeneity within the range of 100-150 kDa. This difference is mainly attributed to the different glycosylation patterns among different cell types or species.

The GPC3 protein is composed of approximately 580 amino acids. Its structural feature is that there is a unique heparan sulfate chain attachment region at the N-terminal, and the C-terminal is anchored to the cell membrane by glycosylphosphatidylinositol. The tertiary structure of this protein forms a specific proteoglycan conformation, enabling it to act as a co-receptor and directly interact with cell signaling molecules (such as Wnt and Hedgehog) through its core protein. At the same time, it regulates the concentration and activity of growth factors through its sugar chain, thereby playing a core role in the regulation of cell proliferation.

Fig. 1 Diagrams of different GPC3-CAR structures.¹

Key structural properties of GPC3:

• Located in the approximately 1MB genomic region of chromosome Xq26.1
• Contains eight highly conserved exon structures
• Protein core sequence encoding 580 amino acids
• As the typical sugar-based phosphatidyl inositol anchor signal sequence

Functions of GPC3

The main function of GPC3 is to act as a co-receptor to regulate the cell growth signaling pathway. However, it is also widely involved in various pathophysiological processes such as embryonic development, tissue regeneration and tumorigenesis.

The interaction between GPC3 and its ligands exhibits a multivalent binding characteristic, which conceptually shares similarities with the synergistic effect of hemoglobin. However, its molecular mechanism involves simultaneously binding multiple signaling molecules (such as Wnt and its co-receptor) to form a signaling complex, thereby significantly amplifying growth-promoting signals. This feature enables it to play a core role in the rapid growth of tumors.

Applications of GPC3 and GPC3 Antibody in Literature

1. Akkermans, Onno, et al. "GPC3-Unc5 receptor complex structure and role in cell migration." Cell 185.21 (2022): 3931-3949. https://doi.org/10.1016/j.cell.2022.09.025

This article reveals the octamer complex structure formed by the central sugar-sugar interaction between GPC3 and Unc5D, which regulates the migration of pyramidal neurons and neuroblastoma cells in the cerebral cortex. Studies have shown that precisely balanced Unc5-GPC3 interactions play a significant guiding role in cancer development and spread.

2. Li, Dinuo, et al. "Targeting GPC3high cancer-associated fibroblasts sensitizing the PD-1 blockage therapy in gastric cancer." Annals of Medicine 55.1 (2023): 2189295. https://doi.org/10.1080/07853890.2023.2189295

Studies have found that Glypican-3 (GPC3) is highly expressed in cancer-related fibroblasts (CAFs) associated with advanced gastric cancer and is associated with poor prognosis and resistance to PD-1 immunotherapy. Targeting CAFs with high GPC3 can effectively sensitize the efficacy of PD-1 inhibitors, indicating that GPC3 is a key prognostic biomarker and potential therapeutic target.

3. Ning, Jing, et al. "GPC3 affects the prognosis of lung adenocarcinoma and lung squamous cell carcinoma." BMC pulmonary medicine 21.1 (2021): 199. https://doi.org/10.1186/s12890-021-01549-9

This study confirmed that GPC3 is significantly highly expressed in non-small cell lung cancer (NSCLC), especially in lung squamous cell carcinoma (LUSC) tissues. The risk scoring model constructed based on GPC3 and its interacting genes can effectively predict the prognosis of lung adenocarcinoma and lung squamous cell carcinoma, providing a new tool for improving the prognosis assessment of patients.

4. Muralidharan, Sujatha, et al. "Glypican-3 (GPC3) is associated with MCPyV-negative status and impaired outcome in Merkel cell carcinoma." Oncotarget 13 (2022): 960. https://doi.org/10.18632/oncotarget.28260

This study found that the expression rate of GPC3 in Merkel cell carcinoma reached 67.7%, and it was particularly common in McPyv-negative cases. GPC3 positivity is an independent risk factor for disease-specific mortality, and its high expression is significantly associated with poor prognosis, suggesting that it can serve as a potential immunotherapy target.

5. Qin, Lijuan, et al. "GPC3 and PEG10 peptides associated with placental gp96 elicit specific T cell immunity against hepatocellular carcinoma." Cancer Immunology, Immunotherapy 72.12 (2023): 4337-4354. https://doi.org/10.1007/s00262-023-03569-2

Research has found that placental molecular chaperone gp96 can bind to antigenic peptides such as GPC3. The GPC3 polypeptide presented by gp96 can induce specific T-cell responses and significantly inhibit the growth of liver cancer. This reveals the mechanism by which placental-derived GPC3 acts as a tumor rejection antigen, laying the foundation for the development of GPC3-based peptide vaccines.

Creative Biolabs: GPC3 Antibodies for Research

Creative Biolabs specializes in the production of high-quality GPC3 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom GPC3 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our GPC3 antibodies, custom preparations, or technical support, contact us at email.