Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P.O., Kochi, Kerala, 682041, India.
Department of Biochemistry, Sree Narayana College, Kollam, Kerala, 691001, India.
Eur J Med Res. 2024 Oct 5;29(1):490. doi: 10.1186/s40001-024-02073-2.
Glypican-3 (GPC-3) is predominantly found in the placenta and fetal liver, with limited expression in adult tissues. Its re-expression in hepatocellular carcinoma (HCC) and secretion into the serum highlights its potential as a diagnostic marker. GPC-3 is involved in important cellular processes such as proliferation, metastasis, apoptosis, and epithelial-mesenchymal transition through various signaling pathways including Wnt, IGF, YAP, and Hedgehog. To review the structure, biosynthesis, and post-translational modifications of GPC-3, and to elucidate its signaling mechanisms and role as a pro-proliferative protein in HCC, emphasizing its diagnostic and therapeutic potential. A comprehensive literature review was conducted, focusing on the expression of GPC-3 in various tumors, with a special emphasis on HCC. The review synthesized findings from experimental studies and clinical trials, analyzing the overexpression of GPC-3 in HCC, its differentiation from other liver diseases, and its potential as a diagnostic and therapeutic target. GPC-3 overexpression in HCC is linked to aggressive tumor behavior and poor prognosis, including shorter overall and disease-free survival. Additionally, GPC-3 has emerged as a promising therapeutic target. Ongoing investigations, including immunotherapies such as monoclonal antibodies and CAR-T cell therapies, demonstrate potential in inhibiting tumor growth and improving clinical outcomes. The review details the multifaceted roles of GPC-3 in tumorigenesis, including its impact on tumor-associated macrophages, glucose metabolism, and epithelial-mesenchymal transition, all contributing to HCC progression. GPC-3's re-expression in HCC and its involvement in key tumorigenic processes underscore its value as a biomarker for early diagnosis and a target for therapeutic intervention. Further research is warranted to fully exploit GPC-3's diagnostic and therapeutic potential in HCC management.
磷脂酰聚糖-3（GPC-3）主要存在于胎盘和胎儿肝脏中，在成人组织中的表达有限。其在肝细胞癌（HCC）中的重新表达和分泌到血清中突出了其作为诊断标志物的潜力。GPC-3 通过各种信号通路（包括 Wnt、IGF、YAP 和 Hedgehog）参与重要的细胞过程，如增殖、转移、凋亡和上皮-间充质转化。为了综述 GPC-3 的结构、生物合成和翻译后修饰，并阐明其信号机制及其作为 HCC 促增殖蛋白的作用，强调其诊断和治疗潜力。进行了全面的文献综述，重点关注 GPC-3 在各种肿瘤中的表达，特别强调 HCC。该综述综合了实验研究和临床试验的发现，分析了 GPC-3 在 HCC 中的过表达、其与其他肝病的区别以及作为诊断和治疗靶点的潜力。GPC-3 在 HCC 中的过表达与侵袭性肿瘤行为和不良预后相关，包括总生存期和无病生存期缩短。此外，GPC-3 已成为有前途的治疗靶点。正在进行的研究，包括免疫疗法，如单克隆抗体和 CAR-T 细胞疗法，显示出抑制肿瘤生长和改善临床结果的潜力。该综述详细介绍了 GPC-3 在肿瘤发生中的多方面作用，包括其对肿瘤相关巨噬细胞、葡萄糖代谢和上皮-间充质转化的影响，所有这些都有助于 HCC 的进展。GPC-3 在 HCC 中的重新表达及其在关键肿瘤发生过程中的参与突出了其作为早期诊断标志物和治疗干预靶点的价值。需要进一步研究以充分利用 GPC-3 在 HCC 管理中的诊断和治疗潜力。
