Abstract
Neuroblastoma (NB) is the most common extracranial 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-NBE(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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1394-1406 |
| Number of pages | 13 |
| Journal | International Journal of Oncology |
| Volume | 49 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 1 2016 |
| Externally published | Yes |
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Keywords
- Angiogenesis
- CAM chorioallantoic-membrane
- Neuroblastoma
- Radiation miR-410
- SPARC
- Vascular endothelial growth factor
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
SPARC overexpression combined with radiation retards angiogenesis by suppressing VEGF-A via miR410 in human neuroblastoma cells. / Boyineni, Jerusha; Tanpure, Smita; Gnanamony, Manu; Antony, Reuben; Fern�ndez, Karen S.; Lin, Julian; Pinson, David; Gondi, Christopher S.
In: International Journal of Oncology, Vol. 49, No. 4, 01.10.2016, p. 1394-1406.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SPARC overexpression combined with radiation retards angiogenesis by suppressing VEGF-A via miR410 in human neuroblastoma cells
AU - Boyineni, Jerusha
AU - Tanpure, Smita
AU - Gnanamony, Manu
AU - Antony, Reuben
AU - Fern�ndez, Karen S.
AU - Lin, Julian
AU - Pinson, David
AU - Gondi, Christopher S.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Neuroblastoma (NB) is the most common extracranial 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-NBE(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.
AB - Neuroblastoma (NB) is the most common extracranial 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-NBE(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.
KW - Angiogenesis
KW - CAM chorioallantoic-membrane
KW - Neuroblastoma
KW - Radiation miR-410
KW - SPARC
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=84990028160&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84990028160&partnerID=8YFLogxK
U2 - 10.3892/ijo.2016.3646
DO - 10.3892/ijo.2016.3646
M3 - Article
C2 - 27498840
AN - SCOPUS:84990028160
VL - 49
SP - 1394
EP - 1406
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 4
ER -