ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Targeting Podoplanin for the Treatment of Osteosarcoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 28 citations in OpenAlex.
- Platelet-Prostate cancer crosstalk driving disparities and therapeutic vulnerabilities.Discover oncology · 2026Review
- SHP2 promotes osteosarcoma via regulating STAT3/TET3/HOXB2 signaling.Scientific reports · 2026Article
- Paired single cell analysis reveals chemotherapy resistance in osteosarcoma.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- Gut-derivedmSystems · 2025Article
- Antitumor Activities by a Humanized Cancer-Specific Anti-Podoplanin Monoclonal Antibody humPMab-117 Against Human Tumors.Cancer science · 2025Article
- Article
- Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.Journal of biomedical science · 2025Review
- Xenografting Human Musculoskeletal Sarcomas in Mice, Chick Embryo, and Zebrafish: How to Boost Translational Research.Biomedicines · 2024Review
- Targeting pathogenic fibroblast-like synoviocyte subsets in rheumatoid arthritis.Arthritis research & therapy · 2024Review
- Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review.World journal of hepatology · 2024Review
- C-type lectin-like receptor 2: roles and drug target.Thrombosis journal · 2024Review
- Antipodoplanin antibody enhances the antitumor effects of CTLA-4 blockade against malignant mesothelioma by natural killer cells.Cancer science · 2024Article
- Sorafenib inhibits doxorubicin-induced PD-L1 upregulation to improve immunosuppressive microenvironment in Osteosarcoma.Journal of cancer research and clinical oncology · 2023Article
- Macrophage Repolarization as a Therapeutic Strategy for Osteosarcoma.International journal of molecular sciences · 2023Review
- Molecular mechanisms of osteosarcoma metastasis and possible treatment opportunities.Frontiers in oncology · 2023Review
- Non-Coding RNAs of Extracellular Vesicles: Key Players in Organ-Specific Metastasis and Clinical Implications.Cancers · 2022Review
- A Cohort Study to Evaluate the Efficacy and Value of CT Perfusion Imaging in Patients with Metastatic Osteosarcoma after Chemotherapy.Computational and mathematical methods in medicine · 2022Article
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20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeOsteosarcoma, the most common bone malignancy in children, has a poor prognosis, especially when the tumor metastasizes to the lungs. Therefore, novel therapeutic strategies targeting both proliferation and metastasis of osteosarcoma are required. Podoplanin (PDPN) is expressed by various tumors and is associated with tumor-induced platelet activation via its interaction with C-type lectin-like receptor 2 (CLEC-2) on platelets. We previously found that PDPN contributed to osteosarcoma growth and metastasis through platelet activation; thus, in this study, we developed an anti-PDPN humanized antibody and evaluated its effect on osteosarcoma growth and metastasis. EXPERIMENTAL
designNine osteosarcoma cell lines and two osteosarcoma patient-derived cells were collected, and we evaluated the efficacy of the anti-DPN-neutralizing antibody PG4D2 and the humanized anti-PDPN antibody AP201, which had IgG4 framework region. The antitumor and antimetastasis effect of PG4D2 and AP201 were examined in vitro and in vivo. In addition, growth signaling by the interaction between PDPN and CLEC-2 was analyzed using phospho-RTK (receptor tyrosine kinase) array, growth assay, or immunoblot analysis under the supression of RTKs by knockout and inhibitor treatment.
resultsWe observed that PG4D2 treatment significantly suppressed tumor growth and pulmonary metastasis in osteosarcoma xenograft models highly expressing PDPN. The contribution of PDGFR activation by activated platelet releasates to osteosarcoma cell proliferation was confirmed, and the humanized antibody, AP201, suppressed in vivo osteosarcoma growth and metastasis without significant adverse events.
conclusionsTargeting PDPN with a neutralizing antibody against PDPN-CLEC-2 without antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity is a novel therapeutic strategy for PDPN-positive osteosarcoma.
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