GPC3 is a member of the heparan sulfate proteoglycan family, primarily involved in cell proliferation, differentiation, migration, and apoptosis. This protein is expressed in healthy fetal liver and kidneys but is nearly absent in adult tissues. In contrast, GPC3 is specifically highly expressed in 70% to 80% of hepatocellular carcinomas (HCC) and is also found at low levels in other tumors such as ovarian clear cell carcinoma, melanoma, and lung squamous cell carcinoma. Studies indicate that GPC3 is closely associated with the occurrence, metastasis, and prognosis of HCC. The GPC3 gene is located on the X chromosome at Xq26, encoding 580 amino acids with a core protein molecular weight of approximately 70 kDa. The protein is cleaved by furin protease between Arg358 and Cys359, producing two subunits linked by disulfide bonds. The membrane-bound form of GPC3 can secrete the N-terminal region as a soluble protein into the bloodstream, while the mature GPC3 heterodimer is anchored to the cell surface via a GPI anchor. Alexa Fluor 647-labeled GPC3 His-tagged protein can be used for quantitative detection of GPC3 expression levels and binding activity, providing a technical tool for liver cancer research.
During embryonic and fetal development, GPC3 is highly expressed in placental and liver tissues, exerting a negative regulatory role. In HCC tissues, however, highly expressed GPC3 promotes tumorigenesis and metastasis. Research shows that GPC3 can activate the canonical Wnt/β-catenin signaling pathway to stimulate the growth of liver cancer cells. Upregulation of GPC3 expression also facilitates HCC metastasis, with studies revealing that increased GPC3 expression in tumor tissues correlates closely with epithelial-mesenchymal transition markers and cancer vascular invasion. GPC3 plays distinct roles during different developmental stages in humans, and its overexpression in adult tissues can drive tumor initiation and metastasis. Thus, GPC3 has emerged as an ideal diagnostic and therapeutic target for HCC. Alexa Fluor 647-labeled GPC3 His-tagged protein can be used to investigate interactions between GPC3 and Wnt signaling pathway-related molecules, providing quantitative analytical tools for mechanistic studies.
Since membrane-bound GPC3 on liver cancer cells can be cleaved by furin protease or lipase to form soluble GPC3 protein, circulating GPC3 in the blood serves as a biomarker for early HCC diagnosis. Compared to the traditional biomarker alpha-fetoprotein (AFP), GPC3 exhibits higher diagnostic sensitivity for HCC. Soluble GPC3 protein can be detected in approximately 50% of AFP-negative HCC patients, confirming its value as a serological biomarker. GPC3 can also be used as an immunohistochemical biomarker for HCC diagnosis, with about 72% of HCC patients testing positive for GPC3, while normal liver tissue and benign liver lesions show negligible or very low detection levels. Additionally, GPC3 serves as a potential biomarker for predicting postoperative tumor recurrence in HCC patients. Patients with low GPC3 expression have better prognoses, whereas high GPC3 expression or a shift from low to high expression is considered a warning sign of cancer recurrence.
GC33 is the first humanized monoclonal antibody targeting GPC3, but clinical trial data indicate that GC33 cannot completely eliminate HCC cells. YP7 is a novel humanized GPC3 antibody with high affinity for liver cancer cells, and both in vitro and in vivo experiments have demonstrated its tumor-inhibiting activity. HN3 can suppress the growth of HCC cell lines and xenografts by binding to both the N- and C-termini of GPC3. These antibodies primarily exert their antitumor effects through antibody-dependent cell-mediated cytotoxicity. Alexa Fluor 647-labeled GPC3 His-tagged protein can be used to evaluate the binding affinity of different GPC3 antibodies to their antigens, providing quantitative data for antibody screening and optimization.
As powerful extensions of monoclonal antibody therapies, CAR-T cells and bispecific antibodies have achieved exciting preclinical results in tumor immunotherapy. In HCC xenograft models constructed in immunodeficient mice, GPC3 CAR-T cells effectively inhibited tumor growth. ERY974, a bispecific antibody targeting GPC3 and CD3, successfully demonstrated killing effects against GPC3-positive xenografts in mouse models. Other bispecific antibodies targeting GPC3 and CD3 similarly mediated the killing of GPC3-positive cell lines and in vivo xenografts. Based on preclinical data, multiple GPC3 CAR-T and bispecific antibody projects are currently undergoing clinical studies. These therapeutic strategies redirect T cells to GPC3-positive tumor cells, achieving specific killing. Alexa Fluor 647-labeled GPC3 His-tagged protein can be used to detect the binding capacity of CAR-T cells to GPC3 antigens, validating their functional activity.
Nanjing UA-BioTech Co., Ltd. (UA-Bio) has independently developed "Alexa Fluor 647-Labeled GPC3 His Tag Protein, Human" (Catalog No.: UA011279), a high-performance far-red fluorescent probe specifically designed for glypican-3 (GPC3) targeting research and multicolor flow cytometry analysis. This protein is human-derived GPC3 with a His tag and Alexa Fluor 647 fluorescent labeling, capable of efficiently binding to anti-GPC3 antibodies or affinity ligands. It provides a stable and reliable standardized tool for applications such as CAR-T cell therapy evaluation, antibody drug screening, and multiparameter analysis of liver cancer biomarkers.
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Nanjing UA-BioTech Co., Ltd. remains committed to providing cutting-edge, high-quality core reagents and tools for immunology, cell therapy, and innovative drug development. For detailed technical parameters, validation data, or specific application inquiries regarding "Alexa Fluor 647-Labeled GPC3 His Tag Protein, Human" (Catalog No.: UA011279), please feel free to contact us.
