Related Experiment Video
Updated: Aug 26, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Inhibition of sphingolipid metabolism in osteosarcoma protects against CD151-mediated tumorigenicity
Hongsheng Wang1,2, Xinmeng Jin1,2, Yangfeng Zhang1,2
1Department of Orthopedics, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
Abstract:
Osteosarcoma is the most common primary bone tumor, with a poor prognosis owing to the lack of efficient molecular-based targeted therapies. Previous studies have suggested an association between CD151 and distinct consequences in osteosarcoma tumorigenicity. However, the potential of CD151 as a therapeutic target has not yet been sufficiently explored. Here, we performed integrated transcriptomic and metabolomic analyses of osteosarcoma and identified sphingolipid metabolism as the top CD151-regulated pathway. CD151 regulates sphingolipid metabolism primarily through SPTCL1, the first rate-limiting enzyme in sphingolipid biosynthesis. Mechanistically, depletion of CD151 enhanced c-myc polyubiquitination and subsequent degradation. c-myc is vital for the transcriptional activation of SPTLC1. Functionally, sphingolipid synthesis and the SPTLC1 inhibitor, myriocin, significantly suppressed the clonogenic growth of CD151-overexpression cells. Importantly, myriocin selectively restrained CD151-high expression tumor growth in preclinical patient-derived xenograft models. Collectively, these data establish that CD151 is a key mediator of sphingolipid metabolism and provide a new approach to developing novel CD151-based targeted therapies for osteosarcoma.
Insights
CD151 regulates sphingolipid metabolism in osteosarcoma, a common bone cancer. Targeting this pathway with myriocin shows promise for new CD151-based therapies.
Area of Science:
- Oncology
- Molecular Biology
- Metabolomics
Background:
- Osteosarcoma is the most common primary bone tumor with a poor prognosis.
- Lack of effective molecular-targeted therapies necessitates novel treatment strategies.
- Previous studies suggest CD151 influences osteosarcoma tumorigenicity, but its therapeutic potential is underexplored.
Purpose of the Study:
- To investigate the role of CD151 in osteosarcoma.
- To identify CD151-regulated molecular pathways.
- To explore CD151 as a potential therapeutic target for osteosarcoma.
Main Methods:
- Integrated transcriptomic and metabolomic analyses of osteosarcoma.
- Investigated CD151 regulation of sphingolipid metabolism via SPTLC1.
- Assessed the impact of CD151 depletion on c-myc stability.
- Evaluated the efficacy of sphingolipid synthesis inhibition (myriocin) in vitro and in vivo.
Main Results:
- Sphingolipid metabolism identified as the top CD151-regulated pathway.
- CD151 regulates sphingolipid biosynthesis through SPTLC1.
- CD151 depletion leads to c-myc degradation.
- Myriocin suppressed CD151-overexpressing osteosarcoma cell growth and tumor progression in xenograft models.
Conclusions:
- CD151 is a key mediator of sphingolipid metabolism in osteosarcoma.
- Targeting CD151-regulated sphingolipid metabolism offers a novel therapeutic strategy.
- Myriocin demonstrates potential as a targeted therapy for CD151-high osteosarcoma.
More Related Videos
07:31A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
11:15A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018