Limits...
Apurinic/apyrimidinic endonuclease 1 regulates angiogenesis in a transforming growth factor β-dependent manner in human osteosarcoma.

Jiang X, Shan J, Dai N, Zhong Z, Qing Y, Yang Y, Zhang S, Li C, Sui J, Ren T, Li M, Wang D - Cancer Sci. (2015)

Bottom Line: In addition, APE1-siRNA led to suppression of angiogenesis in vitro based on HUVECs in Transwell and Matrigel tube formation assays.Reduced secretory protein level of TGFβ of culture medium also resulted in decreased phosphorylation of Smad3 of HUVECs.In a mouse xenograft model, siRNA-mediated silencing of APE1 downregulated TGFβ expression, tumor size, and MVD.

View Article: PubMed Central - PubMed

Affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical expression of apurinic/apyrimidinic endonuclease 1 (APE1), transforming growth factor β (TGFβ), and CD34 in human osteosarcoma. Magnification, ×200 magnification. Left images, high expression of APE1, TGFβ1, and microvessel density staining in an osteoblastic osteosarcoma patient. Right images, representative low expression of APE1, TGFβ1, and microvessel density staining in a fibroblastic osteosarcoma patient.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4638009&req=5

fig01: Immunohistochemical expression of apurinic/apyrimidinic endonuclease 1 (APE1), transforming growth factor β (TGFβ), and CD34 in human osteosarcoma. Magnification, ×200 magnification. Left images, high expression of APE1, TGFβ1, and microvessel density staining in an osteoblastic osteosarcoma patient. Right images, representative low expression of APE1, TGFβ1, and microvessel density staining in a fibroblastic osteosarcoma patient.

Mentions: To investigate the potential correlation between APE1, TGFβ1, and CD34 in osteosarcoma patients, 80 osteosarcoma tissues were immunohistochemically stained. Representative IHC staining with high and low expression of APE1, TGFβ1, and CD34 in osteosarcoma patients are shown in Figure 1. APE1 staining was generally localized in both the nucleus and cytoplasm, and 55 cases showed high APE1 expression levels (68.75%). The TGFβ1 staining was mainly localized in the cytoplasm with high expression observed in 31 cases (38.75%). CD34 staining was mostly localized in the membrane and cytoplasm of vascular endothelial cells in the tumor stroma, and was positive on endothelial cells representing the microvessel. Thirty-four cases had MVD surpassing 37.62 (42.50%). Due to the high expression of APE1 and TGFβ, which was postulated to be correlated with high MVD, the investigation was carried out in osteosarcoma tissues. The expression of these three proteins was positively correlated to each other and the results are presented in Table1. The Cox hazard probability regression model was used to evaluate the potential prognostic factors. As shown in Figure 2, the 2- and 5-year survival rates of osteosarcoma patients were 33.8% and 18.3%, respectively. The baseline patient characteristics (Table2) were similar to a previous report from our group. The data revealed that TGFβ, MVD, and tumor size were important prognostic factors for osteosarcoma. APE1 was excluded in the final model, suggesting its prognostic effect may be dependent on other factors. According to the hazard ratio, the rank of effectiveness of these prognostic factors was TGFβ > tumor size > MVD (Table3).


Apurinic/apyrimidinic endonuclease 1 regulates angiogenesis in a transforming growth factor β-dependent manner in human osteosarcoma.

Jiang X, Shan J, Dai N, Zhong Z, Qing Y, Yang Y, Zhang S, Li C, Sui J, Ren T, Li M, Wang D - Cancer Sci. (2015)

Immunohistochemical expression of apurinic/apyrimidinic endonuclease 1 (APE1), transforming growth factor β (TGFβ), and CD34 in human osteosarcoma. Magnification, ×200 magnification. Left images, high expression of APE1, TGFβ1, and microvessel density staining in an osteoblastic osteosarcoma patient. Right images, representative low expression of APE1, TGFβ1, and microvessel density staining in a fibroblastic osteosarcoma patient.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4638009&req=5

fig01: Immunohistochemical expression of apurinic/apyrimidinic endonuclease 1 (APE1), transforming growth factor β (TGFβ), and CD34 in human osteosarcoma. Magnification, ×200 magnification. Left images, high expression of APE1, TGFβ1, and microvessel density staining in an osteoblastic osteosarcoma patient. Right images, representative low expression of APE1, TGFβ1, and microvessel density staining in a fibroblastic osteosarcoma patient.
Mentions: To investigate the potential correlation between APE1, TGFβ1, and CD34 in osteosarcoma patients, 80 osteosarcoma tissues were immunohistochemically stained. Representative IHC staining with high and low expression of APE1, TGFβ1, and CD34 in osteosarcoma patients are shown in Figure 1. APE1 staining was generally localized in both the nucleus and cytoplasm, and 55 cases showed high APE1 expression levels (68.75%). The TGFβ1 staining was mainly localized in the cytoplasm with high expression observed in 31 cases (38.75%). CD34 staining was mostly localized in the membrane and cytoplasm of vascular endothelial cells in the tumor stroma, and was positive on endothelial cells representing the microvessel. Thirty-four cases had MVD surpassing 37.62 (42.50%). Due to the high expression of APE1 and TGFβ, which was postulated to be correlated with high MVD, the investigation was carried out in osteosarcoma tissues. The expression of these three proteins was positively correlated to each other and the results are presented in Table1. The Cox hazard probability regression model was used to evaluate the potential prognostic factors. As shown in Figure 2, the 2- and 5-year survival rates of osteosarcoma patients were 33.8% and 18.3%, respectively. The baseline patient characteristics (Table2) were similar to a previous report from our group. The data revealed that TGFβ, MVD, and tumor size were important prognostic factors for osteosarcoma. APE1 was excluded in the final model, suggesting its prognostic effect may be dependent on other factors. According to the hazard ratio, the rank of effectiveness of these prognostic factors was TGFβ > tumor size > MVD (Table3).

Bottom Line: In addition, APE1-siRNA led to suppression of angiogenesis in vitro based on HUVECs in Transwell and Matrigel tube formation assays.Reduced secretory protein level of TGFβ of culture medium also resulted in decreased phosphorylation of Smad3 of HUVECs.In a mouse xenograft model, siRNA-mediated silencing of APE1 downregulated TGFβ expression, tumor size, and MVD.

View Article: PubMed Central - PubMed

Affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China.

No MeSH data available.


Related in: MedlinePlus