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Hypoxia and free radicals: Role in tumor progression and the use of engineering-based platforms to address these relationships
Free radical biology & medicine
  • Abigail Hielscher, Philadelphia College of Osteopathic Medicine
  • S. Gerecht
Document Type
Article
Publication Date
10-1-2014
Abstract

Hypoxia is a feature of all solid tumors, contributing to tumor progression and therapy resistance. Through stabilization of the hypoxia-inducible factor 1 alpha (HIF-1alpha), hypoxia activates the transcription of a number of genes that sustain tumor progression. Since the seminal discovery of HIF-1alpha as a hypoxia-responsive master regulator of numerous genes and transcription factors, several groups have reported a novel mechanism whereby hypoxia mediates stabilization of HIF-1alpha. This process occurs as a result of hypoxia-generated reactive oxygen species (ROS), which, in turn, stabilize the expression of HIF-1alpha. As a result, a number of genes regulating tumor growth are expressed, fueling ongoing tumor progression. In this review, we outline a role for hypoxia in generating ROS and additionally define the mechanisms contributing to ROS-induced stabilization of HIF-1alpha.We further explore how ROS-induced HIF-1alpha stabilization contributes to tumor growth, angiogenesis, metastasis, and therapy response. We discuss a future outlook, describing novel therapeutic approaches for attenuating ROS production while considering how these strategies should be carefully selected when combining with chemotherapeutic agents. As engineering-based approaches have been more frequently utilized to address biological questions, we discuss opportunities whereby engineering techniques may be employed to better understand the physical and biochemical factors controlling ROS expression. It is anticipated that an improved understanding of the mechanisms responsible for the hypoxia/ROS/HIF-1alpha axis in tumor progression will yield the development of better targeted therapies.

Comments

This article was published in Free radical biology & medicine, Volume 79C, Pages 281-291.

The published version is available at http://dx.doi.org/10.1016/j.freeradbiomed.2014.09.015.

Copyright © 2014 Elsevier.

Citation Information
Abigail Hielscher and S. Gerecht. "Hypoxia and free radicals: Role in tumor progression and the use of engineering-based platforms to address these relationships" Free radical biology & medicine Vol. 79 (2015) (2014) p. 281 - 291
Available at: http://works.bepress.com/abigail_hielscher/1/