ArticleJournal of bone oncology2021
Identification of GPC3 mutation and upregulation in a multidrug resistant osteosarcoma and its spheroids as therapeutic target.
Article in Journal of bone oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin + Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Personalized prediction of chemotherapy efficacy in osteosarcoma through patient-derived organoids: correlation with survival and tumor proliferation potential.Journal of experimental & clinical cancer research : CR · 2025Article
- Engineering Osteosarcoma In Vitro: From Traditional Models to Biofabricated Platforms for Precision Medicine.ACS omega · 2025Review
- Establishment of patient-derived 3D in vitro models of sarcomas: literature review and guidelines on behalf of the FORTRESS working group.Neoplasia (New York, N.Y.) · 2025Review
- Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy.British journal of cancer · 2024Article
- What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes?Pflugers Archiv : European journal of physiology · 2024Review
- 3D Models of Sarcomas: The Next-generation Tool for Personalized Medicine.Phenomics (Cham, Switzerland) · 2024Review
- Review
- RUNX2 and Cancer.International journal of molecular sciences · 2023Review
- Dual Inhibition of BRAF-MAPK and STAT3 Signaling Pathways in Resveratrol-Suppressed Anaplastic Thyroid Cancer Cells with BRAF Mutations.International journal of molecular sciences · 2022Article
- Frequently expressed glypican-3 as a promising novel therapeutic target for osteosarcomas.Cancer science · 2022Article
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Authors and funding
14 authors.
Funding
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Abstract
backgroundDrug resistance and the lack of molecular therapeutic target are the main challenges in the management of osteosarcomas (OSs). Identification of novel genetic alteration(s) related with OS recurrence and chemotherapeutic resistance would be of scientific and clinical significance.
methodsTo identify potential genetic alterations related with OS recurrence and chemotherapeutic resistance, the biopsies of a 20-year-old male osteosarcoma patient were collected at primary site (p-OS) and from its metastatic tumor (m-OS) formed after 5 months of adjuvant chemotherapy. Both OS specimens were subjected to cancer-targeted next generation sequencing (NGS) and their cell suspensions were cultured under three-dimensional condition to establish spheroid therapeutic model. Transcript-oriented Sanger sequencing for GPC3, the detected mutated gene, was performed on RNA samples of p-OS and m-OS tissues and spheroids. The effects of anti-GPC3 antibody and its combination with cisplatin on m-OS spheroids were elucidated.
resultsNGS revealed 4 mutations (GPC3, SOX10, MDM4 and MAPK8) and 6 amplifications (MDM2, CDK4, CCND3, RUNX2, GLI1 and FRS2) in p-OS, and 3 mutations (GPC3, SOX10 and EGF) and 10 amplifications (CDK4, CCND3, MDM2, RUNX2, GLI1, FRS2, CARD11, RAC1, SLC16A7 and PMS2) in m-OS. Among those alterations, the mutation abundance of GPC3 was the highest (56.49%) in p-OS and showed 1.54 times increase in m-OS. GPC3 transcript-oriented Sanger sequencing confirmed the mutation at 1046 in Exon 4, and immunohistochemical staining showed increased GPC3 production in m-OS tissues and its spheroids. EdU cell proliferation and Calcein/PI cell viability assays revealed that of the anti-OS first line drugs (doxorubicin, cisplatin, methotrexate, ifosfamide and carboplatin), 10 μM carboplatin exerted the best inhibitory effects on the p-OS but not the m-OS spheroids. 2 μg/mL anti-GPC3 antibody effectively committed m-OS spheroids to death by itself (76.43%) or in combination with cisplatin (92.93%).
conclusionThis study demonstrates increased abundance and up-regulated expression of mutant GPC3 in metastatic osteosarcoma and its spheroids with multidrug resistance. As GPC3-targeting therapy has been used to treat hepatocellular carcinomas and it is also effective to OS PDSs, GPC3 would be a novel prognostic parameter and therapeutic target of osteosarcomas.
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