Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism.

Journal Article (Journal Article)

Vascular recovery or re-angiogenesis after radiotherapy plays a significant role in tumor recurrence, whereas molecular mechanisms of this process remain elusive. In this work, we found that dying glioma cells promoted post-irradiation angiogenesis through a caspase 3 dependent mechanism. Evidence in vitro and in vivo indicated that caspase 3 inhibition undermined proangiogenic effects of dying glioma cells. Proteolytic inactivation of caspase 3 in glioma cells reduced tumorigenicity. Importantly, we identified that NF-κB/COX-2/PGE2 axis acted as downstream signaling of caspase 3, mediating proangiogenic response after irradiation. Additionally, VEGF-A, regulated by caspase 3 possibly through phosphorylated eIF4E, was recognized as another downstream factor participating in the proangiogenic response. In conclusion, these data demonstrated that caspase 3 in dying glioma cells supported the proangiogenic response after irradiation by governing NF-κB/COX-2/PGE2 axis and p-eIF4E/VEGF-A signaling. While inducing caspase 3 activation has been a generally-adopted notion in cancer therapeutics, our study counterintuitively illustrated that caspase 3 activation in dying glioma cells unfavorably supported post-irradiation angiogenesis. This double-edged role of caspase 3 suggested that taming caspase 3 from the opposite side, not always activating it, may provide novel therapeutic strategies due to restricted post-irradiation angiogenesis.

Full Text

Duke Authors

Cited Authors

  • Feng, X; Yu, Y; He, S; Cheng, J; Gong, Y; Zhang, Z; Yang, X; Xu, B; Liu, X; Li, C-Y; Tian, L; Huang, Q

Published Date

  • January 28, 2017

Published In

Volume / Issue

  • 385 /

Start / End Page

  • 12 - 20

PubMed ID

  • 27826040

Pubmed Central ID

  • PMC5323266

Electronic International Standard Serial Number (EISSN)

  • 1872-7980

Digital Object Identifier (DOI)

  • 10.1016/j.canlet.2016.10.042


  • eng

Conference Location

  • Ireland