2. Academic Validation
  3. NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using Larotrectinib

NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using Larotrectinib

  • Life (Basel). 2025 Jan 15;15(1):99. doi: 10.3390/life15010099.
Sheng-Mou Hou 1 2,  Ching-Yuan Cheng 3,  Wei-Li Chen 4,  En-Ming Chang 5,  Chih-Yang Lin 6
Affiliations

Affiliations

  • 1 Department of Research, Taiwan Blood Services Foundation, Taipei 111, Taiwan.
  • 2 The Director's Office, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
  • 3 Division of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
  • 4 Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
  • 5 Department of Respiratory Care, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
  • 6 Translational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
PMID: 39860039 DOI: 10.3390/life15010099
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.

Keywords

NGF; angiogenesis; larotrectinib; miR-29b-3p; osteosarcoma.

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