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Updated: Jul 13, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Anticancer peptides from induced tumor-suppressing cells for inhibiting osteosarcoma cells
Chang-Peng Cui1,2, Qing-Ji Huo1,2, Xue Xiong1,2
1Department of Pharmacology, School of Pharmacy, Harbin Medical University Harbin 150081, Heilongjiang, China.
Abstract:
Osteosarcoma (OS) is the most frequent primary bone cancer, which is mainly suffered by children and young adults. While the current surgical treatment combined with chemotherapy is effective for the early stage of OS, advanced OS preferentially metastasizes to the lung and is difficult to treat. Here, we examined the efficacy of ten anti-OS peptide candidates from a trypsin-digested conditioned medium that was derived from the secretome of induced tumor-suppressing cells (iTSCs). Using OS cell lines, the antitumor capabilities of the peptide candidates were evaluated by assaying the alterations in metabolic activities, proliferation, motility, and invasion of OS cells. Among ten candidates, peptide P05 (ADDGRPFPQVIK), a fragment of aldolase A (ALDOA), presented the most potent OS-suppressing capabilities. Its efficacy was additive with standard-of-care chemotherapeutic agents such as cisplatin and doxorubicin, and it downregulated oncoproteins such as epidermal growth factor receptor (EGFR), Snail, and Src in OS cells. Interestingly, P05 did not present inhibitory effects on non-OS skeletal cells such as mesenchymal stem cells and osteoblast cells. Collectively, this study demonstrated that iTSC-derived secretomes may provide a source for identifying anticancer peptides, and P05 may warrant further evaluations for the treatment of OS.
Insights
Researchers identified a novel peptide, P05, derived from tumor-suppressing cells, showing potent osteosarcoma (OS) suppression. This peptide effectively targets cancer cells without harming healthy bone cells, offering a promising new avenue for OS treatment.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Osteosarcoma (OS) is a primary bone cancer predominantly affecting young individuals.
- Advanced OS often metastasizes to the lungs, posing significant treatment challenges.
- Current treatments combining surgery and chemotherapy are less effective for advanced or metastatic OS.
Purpose of the Study:
- To identify and evaluate novel anti-osteosarcoma (OS) peptide candidates.
- To assess the efficacy of these peptides against OS cell lines.
- To investigate the potential of peptides derived from induced tumor-suppressing cells (iTSCs) for OS therapy.
Main Methods:
- Secretome analysis of iTSCs to derive peptide candidates.
- In vitro evaluation of peptide efficacy on OS cell lines.
- Assays measuring metabolic activity, proliferation, motility, and invasion.
- Assessment of peptide effects on non-OS skeletal cells.
- Analysis of oncoprotein modulation (EGFR, Snail, Src).
Main Results:
- Peptide P05, a fragment of aldolase A (ALDOA), demonstrated the strongest OS-suppressing activity.
- P05 showed additive effects when combined with cisplatin and doxorubicin.
- P05 downregulated key oncoproteins including EGFR, Snail, and Src in OS cells.
- P05 exhibited no inhibitory effects on mesenchymal stem cells or osteoblast cells.
Conclusions:
- iTSC-derived secretomes are a viable source for discovering anticancer peptides.
- Peptide P05 shows significant potential as a targeted therapeutic agent for osteosarcoma.
- P05 warrants further investigation for its clinical application in treating osteosarcoma.
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