NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using Larotrectinib
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...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/15/1/99 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588105932079104 |
|---|---|
| author | Sheng-Mou Hou Ching-Yuan Cheng Wei-Li Chen En-Ming Chang Chih-Yang Lin |
| author_facet | Sheng-Mou Hou Ching-Yuan Cheng Wei-Li Chen En-Ming Chang Chih-Yang Lin |
| author_sort | Sheng-Mou Hou |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-03c5e36ababa40c9bce9955cb75a2505 |
| institution | Kabale University |
| issn | 2075-1729 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj-art-03c5e36ababa40c9bce9955cb75a25052025-01-24T13:38:47ZengMDPI AGLife2075-17292025-01-011519910.3390/life15010099NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using LarotrectinibSheng-Mou Hou0Ching-Yuan Cheng1Wei-Li Chen2En-Ming Chang3Chih-Yang Lin4Department of Research, Taiwan Blood Services Foundation, Taipei 111, TaiwanDivision of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, TaiwanGraduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 100, TaiwanDepartment of Respiratory Care, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, TaiwanTranslational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, TaiwanAngiogenesis 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.https://www.mdpi.com/2075-1729/15/1/99osteosarcomaNGFlarotrectinibangiogenesismiR-29b-3p |
| spellingShingle | Sheng-Mou Hou Ching-Yuan Cheng Wei-Li Chen En-Ming Chang Chih-Yang Lin NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using Larotrectinib Life osteosarcoma NGF larotrectinib angiogenesis miR-29b-3p |
| title | NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using Larotrectinib |
| title_full | NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using Larotrectinib |
| title_fullStr | NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using Larotrectinib |
| title_full_unstemmed | NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using Larotrectinib |
| title_short | NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using Larotrectinib |
| title_sort | ngf trka axis enhances pdgf c mediated angiogenesis in osteosarcoma via mir 29b 3p suppression a potential therapeutic strategy using larotrectinib |
| topic | osteosarcoma NGF larotrectinib angiogenesis miR-29b-3p |
| url | https://www.mdpi.com/2075-1729/15/1/99 |
| work_keys_str_mv | AT shengmouhou ngftrkaaxisenhancespdgfcmediatedangiogenesisinosteosarcomaviamir29b3psuppressionapotentialtherapeuticstrategyusinglarotrectinib AT chingyuancheng ngftrkaaxisenhancespdgfcmediatedangiogenesisinosteosarcomaviamir29b3psuppressionapotentialtherapeuticstrategyusinglarotrectinib AT weilichen ngftrkaaxisenhancespdgfcmediatedangiogenesisinosteosarcomaviamir29b3psuppressionapotentialtherapeuticstrategyusinglarotrectinib AT enmingchang ngftrkaaxisenhancespdgfcmediatedangiogenesisinosteosarcomaviamir29b3psuppressionapotentialtherapeuticstrategyusinglarotrectinib AT chihyanglin ngftrkaaxisenhancespdgfcmediatedangiogenesisinosteosarcomaviamir29b3psuppressionapotentialtherapeuticstrategyusinglarotrectinib |