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Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis.

Publication ,  Journal Article
Feng, X; Tian, L; Zhang, Z; Yu, Y; Cheng, J; Gong, Y; Li, C-Y; Huang, Q
Published in: Oncotarget
October 20, 2015

Cytotoxic radiotherapy unfavorably induces tumor cells to generate various proangiogenic substances, promoting post-irradiation angiogenesis (PIA), which is one of major causes of radiotherapy failure. Though several studies have reported some mechanisms behind PIA, they have not yet described the beginning proangiogenic motivator buried in the irradiated microenvironment. In this work, we revealed that dying tumor cells induced by irradiation prompted PIA via a caspase 3 dependent mechanism. Proteolytic inactivation of caspase 3 in dying tumor cells by transducing a dominant-negative version weakened proangiogenic effects in vitro and in vivo. In addition, inhibition of caspase 3 activity suppressed tumor angiogenesis and tumorigenesis in xenograft mouse model. Importantly, we identified vascular endothelial growth factor (VEGF)-A as a downstream proangiogenic factor regulated by caspase 3 possibly through Akt signaling. Collectively, these findings indicated that besides acting as a key executioner in apoptosis, caspase 3 in dying tumor cells may play a central role in driving proangiogenic response after irradiation. Thus, radiotherapy in combination with caspase 3 inhibitors may be a novel promising therapeutic strategy to reduce tumor recurrence due to restrained PIA.

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Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

October 20, 2015

Volume

6

Issue

32

Start / End Page

32353 / 32367

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Time Factors
  • Signal Transduction
  • Paracrine Communication
  • Neovascularization, Pathologic
  • Mice, Nude
  • Male
  • Humans
  • Human Umbilical Vein Endothelial Cells
  • HT29 Cells
 

Citation

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Feng, X., Tian, L., Zhang, Z., Yu, Y., Cheng, J., Gong, Y., … Huang, Q. (2015). Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis. Oncotarget, 6(32), 32353–32367. https://doi.org/10.18632/oncotarget.5898
Feng, Xiao, Ling Tian, Zhengxiang Zhang, Yang Yu, Jin Cheng, Yanping Gong, Chuan-Yuan Li, and Qian Huang. “Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis.Oncotarget 6, no. 32 (October 20, 2015): 32353–67. https://doi.org/10.18632/oncotarget.5898.
Feng X, Tian L, Zhang Z, Yu Y, Cheng J, Gong Y, et al. Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis. Oncotarget. 2015 Oct 20;6(32):32353–67.
Feng, Xiao, et al. “Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis.Oncotarget, vol. 6, no. 32, Oct. 2015, pp. 32353–67. Pubmed, doi:10.18632/oncotarget.5898.
Feng X, Tian L, Zhang Z, Yu Y, Cheng J, Gong Y, Li C-Y, Huang Q. Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis. Oncotarget. 2015 Oct 20;6(32):32353–32367.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

October 20, 2015

Volume

6

Issue

32

Start / End Page

32353 / 32367

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Time Factors
  • Signal Transduction
  • Paracrine Communication
  • Neovascularization, Pathologic
  • Mice, Nude
  • Male
  • Humans
  • Human Umbilical Vein Endothelial Cells
  • HT29 Cells