Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan that is highly expressed in fetal liver but nearly absent in normal adult liver tissues. However, in hepatocellular carcinoma (HCC), GPC3 is significantly overexpressed in over 70% of cases, with both mRNA and protein levels markedly elevated. Studies have demonstrated that GPC3 overexpression is closely associated with poor prognosis in HCC patients and drives tumorigenesis and progression through activation of multiple signaling pathways, including Wnt/β-catenin and ERK. Given its high specificity in tumor tissues, GPC3 has emerged as an important biomarker for HCC diagnosis, targeted therapy, and immunotherapy.
Luciferase 2 (Luc2) is a codon-optimized firefly luciferase gene with enhanced expression efficiency and bioluminescence intensity, widely used for in vivo bioluminescence imaging. Combining Luc2 reporter gene with GPC3 overexpression enables the construction of GPC3-Luc2 overexpressing cell lines, facilitating real-time tracking of GPC3-positive tumor cells, in vivo tumor growth monitoring, and evaluation of antitumor therapeutic efficacy. For instance, CT26 cell lines stably transfected with GPC3-Luc2 have been applied in drug screening and biological assays. Furthermore, GPC3 promoter-driven luciferase reporter systems provide a powerful tool for studying the transcriptional regulatory mechanisms of GPC3. Therefore, overexpression of the GPC3-Luc2 gene not only facilitates in-depth understanding of the biological functions of GPC3 in hepatocarcinogenesis but also provides a valuable experimental model for targeted therapy research in HCC.