title: SPARC overexpression combined with radiation retards angiogenesis by suppressing VEGF-A via miR‑410 in human neuroblastoma cells.
abstract: 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.
authors: Department of Internal Medicine, University of Illinois College of Medicine, Peoria, IL 61605, USA.
authors: Jerusha
authors: J
authors: Boyineni
authors: Department of Internal Medicine, University of Illinois College of Medicine, Peoria, IL 61605, USA.
authors: Smita
authors: S
authors: Tanpure
authors: Department of Internal Medicine, University of Illinois College of Medicine, Peoria, IL 61605, USA.
authors: Manu
authors: M
authors: Gnanamony
authors: Department of Pediatrics, University of Illinois College of Medicine, Peoria, IL 61605, USA.
authors: Reuben
authors: R
authors: Antony
authors: Department of Pediatrics, University of Illinois College of Medicine, Peoria, IL 61605, USA.
authors: Karen S
authors: KS
authors: Fernández
authors: Department of Neurosurgery, University of Illinois College of Medicine, Peoria, IL 61605, USA.
authors: Julian
authors: J
authors: Lin
authors: Department of Pathology, University of Illinois College of Medicine, Peoria, IL 61605, USA.
authors: David
authors: D
authors: Pinson
authors: Department of Internal Medicine, University of Illinois College of Medicine, Peoria, IL 61605, USA.
authors: Christopher S
authors: CS
authors: Gondi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000628:therapy*; D009447:Neuroblastoma / Q000098:blood supply / Q000235:genetics / Q000628:therapy*; D015676:Osteonectin / Q000235:genetics* / Q000378:metabolism; D011878:Radiotherapy; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; C568527:MIRN410 microRNA, human; D035683:MicroRNAs; D015676:Osteonectin; C577241:SPARC protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A