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Updated: Dec 1, 2025

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Neuropilin and tolloid-like 2 regulates the progression of osteosarcoma
Xuepeng Wang1, Zhenyu Bian1, Changju Hou1
1Department of Orthopedics Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310006, China.
Abstract:
Neuropilin and tolloid-like 2 (NETO2) is aberrantly expressed in various malignancies. However, its role in osteosarcoma (OS) remains to be elucidated. This study aimed to identify the function of NETO2 in OS cells. The expression of NETO2 in sarcoma tissues was determined using the GEPIA database, and the mRNA and protein expression of NETO2 in OS cells and OS tissue was also assessed. The biological effects of NETO2 on OS cells were determined by overexpressing and downregulating NETO2. Cell proliferation, invasion, migration, colony formation, and epithelial-mesenchymal transition in OS cells were evaluated. Consistent with the GEPIA database, expression of NETO2 was upregulated in human OS samples and cell lines. NETO2 overexpression not only promoted the proliferation, colony formation, invasion, and epithelial-mesenchymal transition of OS cells, but also activated the PI3K/AKT signaling. NETO2 downregulation resulted in opposite effects. Furthermore, after using an AKT inhibitor, the effects of NETO2 on OS cells were attenuated. In conclusion, this study showed that NETO2 functions as an oncogene of osteosarcomas by activating the PI3K/AKT pathway.
Insights
Neuropilin and tolloid-like 2 (NETO2) acts as an oncogene in osteosarcoma (OS). Upregulated NETO2 promotes OS cell proliferation and invasion by activating the PI3K/AKT pathway, driving cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Neuropilin and tolloid-like 2 (NETO2) expression is altered in various cancers.
- The specific role of NETO2 in osteosarcoma (OS) pathogenesis is not well understood.
Purpose of the Study:
- To investigate the function and mechanism of NETO2 in osteosarcoma cells.
- To determine if NETO2 acts as an oncogene in osteosarcoma.
Main Methods:
- Assessed NETO2 expression in human OS samples and cell lines using GEPIA database, mRNA, and protein analysis.
- Manipulated NETO2 levels (overexpression and downregulation) in OS cells to evaluate effects on proliferation, invasion, migration, colony formation, and epithelial-mesenchymal transition (EMT).
- Investigated the involvement of the PI3K/AKT signaling pathway and utilized an AKT inhibitor to confirm pathway activation.
Main Results:
- NETO2 expression was significantly upregulated in human osteosarcoma tissues and cell lines.
- NETO2 overexpression enhanced OS cell proliferation, invasion, migration, colony formation, and EMT.
- NETO2 promoted osteosarcoma progression by activating the PI3K/AKT signaling pathway, as evidenced by increased signaling and attenuation of NETO2 effects with an AKT inhibitor.
Conclusions:
- NETO2 functions as an oncogene in osteosarcoma.
- NETO2 promotes osteosarcoma development and progression through activation of the PI3K/AKT signaling pathway.
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