NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential
Sheng-Mou Hou1,2, Ching-Yuan Cheng3, Wei-Li Chen4
1Department of Research, Taiwan Blood Services Foundation, Taipei 111, Taiwan.
Abstract:
Angiogenesis plays a critical role in osteosarcoma (OS) growth and metastasis. While nerve growth factor (NGF) is implicated in cancer progression, its role in OS angiogenesis remains unclear. This study explored NGF's effects on angiogenesis and the underlying molecular mechanisms. Analysis of GEO (GSE16088) data identified five angiogenesis markers significantly upregulated in OS tissues. In vitro experiments demonstrated that NGF enhanced HUVEC tube formation by upregulating platelet-derived growth factor C (PDGF-C) expression and suppressing microRNA-29b-3p (miR-29b-3p). The results of tube formation assays confirmed that NGF stimulation significantly increased the angiogenic capacity of MG63/NGF cells compared to MG63 cells. Furthermore, larotrectinib, a TrkA inhibitor, effectively reduced the migration and invasion abilities of MG63/NGF cells in a dose-dependent manner. These findings suggest that the NGF-TrkA axis promotes PDGF-C-mediated angiogenesis by inhibiting miR-29b-3p signaling. Larotrectinib could serve as a potential therapeutic agent targeting NGF-mediated angiogenesis in OS, offering a promising avenue for treatment.
Insights
Nerve growth factor (NGF) promotes osteosarcoma (OS) angiogenesis by upregulating PDGF-C and inhibiting miR-29b-3p. The TrkA inhibitor larotrectinib shows potential for treating NGF-driven angiogenesis in OS.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Angiogenesis is crucial for osteosarcoma (OS) progression and metastasis.
- The role of nerve growth factor (NGF) in OS angiogenesis is not well understood.
Purpose of the Study:
- To investigate the effect of NGF on osteosarcoma angiogenesis and its molecular mechanisms.
- To identify potential therapeutic targets for NGF-mediated angiogenesis in OS.
Main Methods:
- Analysis of GEO dataset (GSE16088) for angiogenesis markers in OS tissues.
- In vitro experiments using HUVECs and MG63 cells to assess NGF's angiogenic effects.
- Investigated the role of platelet-derived growth factor C (PDGF-C) and microRNA-29b-3p (miR-29b-3p).
- Utilized larotrectinib, a TrkA inhibitor, to evaluate its impact on cell migration and invasion.
Main Results:
- NGF significantly enhanced HUVEC tube formation, indicating increased angiogenic capacity.
- NGF upregulated PDGF-C expression and suppressed miR-29b-3p in OS cells.
- Larotrectinib dose-dependently inhibited the migration and invasion of MG63/NGF cells.
- The NGF-TrkA axis was found to promote PDGF-C-mediated angiogenesis via miR-29b-3p inhibition.
Conclusions:
- The NGF-TrkA signaling pathway plays a key role in promoting osteosarcoma angiogenesis.
- Targeting the NGF-TrkA axis, potentially with larotrectinib, offers a promising therapeutic strategy for OS.
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