SPARC overexpression combined with radiation retards angiogenesis by suppressing VEGF-A via miR-410 in human neuroblastoma cells

Autor: Jerusha Boyineni, Manu Gnanamony, Christopher S. Gondi, David M. Pinson, Julian Lin, Reuben Antony, Smita Tanpure, Karen S. Fernández
Rok vydání: 2016
Předmět:
Vascular Endothelial Growth Factor A
0301 basic medicine
Cancer Research
Angiogenesis
Cell
Angiogenesis Inhibitors
Biology
Neovascularization
angiogenesis
Mice
Neuroblastoma
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
CAM chorioallantoic-membrane
Cell Line
Tumor
medicine
Animals
Humans
Osteonectin
radiation miR-410
vascular endothelial growth factor
Neovascularization
Pathologic
Radiotherapy
Oncogene
SPARC
Articles
Genetic Therapy
Cell cycle
medicine.disease
Xenograft Model Antitumor Assays
Molecular biology
Gene Expression Regulation
Neoplastic
Vascular endothelial growth factor
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
Oncology
chemistry
Cell culture
030220 oncology & carcinogenesis
Cancer research
medicine.symptom
Neoplasm Transplantation
Zdroj: International Journal of Oncology
ISSN: 1791-2423
1019-6439
DOI: 10.3892/ijo.2016.3646
Popis: Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and despite aggressive therapy survival rates remain low. One of the contributing factors for low survival rates is aggressive tumor angiogenesis, which is known to increase due to radiation, one of the standard therapies for neuroblastoma. Therefore, targeting tumor angiogenesis can be a viable add-on therapy for the treatment of neuroblastomas. In the present study, we demonstrate that overexpression of secreted protein acidic and rich in cysteine (SPARC) suppresses radiation induced angiogenesis in SK-N‑BE(2) and NB1691 neuroblastoma cells. We observed that overexpression of SPARC in SK-N-BE(2) and NB1691 cells reduced radiation induced angiogenesis in an in vivo mouse dorsal skin model and an ex vivo chicken CAM (chorioallantoic-membrane) model and also reduced tumor size in subcutaneous mouse tumor models of NB. We also observed that SPARC overexpression reduces VEGF-A expression, in SK-N-BE(2) and NB1691 NB cells via miR-410, a VEGF-A targeting microRNA. SPARC overexpression alone or in combination with miR-410 and radiation was shown to be effective at reducing angiogenesis. Moreover, addition of miR-410 inhibitors reversed SPARC mediated inhibition of VEGF-A in NB1691 cells but not in SK-N-BE(2) NB cells. In conclusion, the present study demonstrates that the overexpression of SPARC in combination with radiation reduced tumor angiogenesis by downregulating VEGF-A via miR-410.
Databáze: OpenAIRE
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