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Hyaluronic acid hydrogel stiffness and oxygen tension affect cancer cell fate and endothelial sprouting.

Publication ,  Journal Article
Shen, Y-I; Abaci, HE; Krupsi, Y; Weng, L-C; Burdick, JA; Gerecht, S
Published in: Biomaterials science
May 2014

Three-dimensional (3D) tissue culture models may recapitulate aspects of the tumorigenic microenvironment in vivo, enabling the study of cancer progression in vitro. Both hypoxia and matrix stiffness are known to regulate tumor growth. Using a modular culture system employing an acrylated hyaluronic acid (AHA) hydrogel, three hydrogel matrices with distinctive degrees of viscoelasticity - soft (78±16 Pa), medium (309± 57 Pa), and stiff (596± 73 Pa) - were generated using the same concentration of adhesion ligands. Oxygen levels within the hydrogel in atmospheric (21 %), hypoxic (5 %), and severely hypoxic (1 %) conditions were assessed with a mathematical model. HT1080 fibrosarcoma cells, encapsulated within the AHA hydrogels in high densities, generated nonuniform oxygen distributions, while lower cell densities resulted in more uniform oxygen distributions in the atmospheric and hypoxic environments. When we examined how varying viscoelasticity in atmospheric and hypoxic environments affects cell cycles and the expression of BNIP3 and BNIP3L (autophagy and apoptosis genes), and GLUT-1 (a glucose transport gene), we observed that HT1080 cells in 3D hydrogel adapted better to hypoxic conditions than those in a Petri dish, with no obvious correlation to matrix viscoelasticity, by recovering rapidly from possible autophagy/apoptotic events and alternating metabolism mechanisms. Further, we examined how HT1080 cells cultured in varying viscoelasticity and oxygen tension conditions affected endothelial sprouting and invasion. We observed that increased matrix stiffness reduced endothelial sprouting and invasion in atmospheric conditions; however, we observed increased endothelial sprouting and invasion under hypoxia at all levels of matrix stiffness with the upregulation of vascular endothelial growth factor (VEGF) and angiopoeitin-1 (ANG-1). Overall, HT1080 cells encapsulated in the AHA hydrogels under hypoxic stress recovered better from apoptosis and demonstrated greater angiogenic induction. Thus, we propose that oxygen tension more profoundly influences cell fate and the angiogenic potential of 3D cultured HT1080 fibrosarcoma cells than does matrix stiffness.

Duke Scholars

Published In

Biomaterials science

DOI

EISSN

2047-4849

ISSN

2047-4830

Publication Date

May 2014

Volume

2

Issue

5

Start / End Page

655 / 665

Related Subject Headings

  • 4003 Biomedical engineering
  • 3206 Medical biotechnology
  • 1004 Medical Biotechnology
  • 0601 Biochemistry and Cell Biology
  • 0304 Medicinal and Biomolecular Chemistry
 

Citation

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MLA
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Shen, Y.-I., Abaci, H. E., Krupsi, Y., Weng, L.-C., Burdick, J. A., & Gerecht, S. (2014). Hyaluronic acid hydrogel stiffness and oxygen tension affect cancer cell fate and endothelial sprouting. Biomaterials Science, 2(5), 655–665. https://doi.org/10.1039/c3bm60274e
Shen, Yu-I, Hasan E. Abaci, Yoni Krupsi, Lien-Chun Weng, Jason A. Burdick, and Sharon Gerecht. “Hyaluronic acid hydrogel stiffness and oxygen tension affect cancer cell fate and endothelial sprouting.Biomaterials Science 2, no. 5 (May 2014): 655–65. https://doi.org/10.1039/c3bm60274e.
Shen Y-I, Abaci HE, Krupsi Y, Weng L-C, Burdick JA, Gerecht S. Hyaluronic acid hydrogel stiffness and oxygen tension affect cancer cell fate and endothelial sprouting. Biomaterials science. 2014 May;2(5):655–65.
Shen, Yu-I., et al. “Hyaluronic acid hydrogel stiffness and oxygen tension affect cancer cell fate and endothelial sprouting.Biomaterials Science, vol. 2, no. 5, May 2014, pp. 655–65. Epmc, doi:10.1039/c3bm60274e.
Shen Y-I, Abaci HE, Krupsi Y, Weng L-C, Burdick JA, Gerecht S. Hyaluronic acid hydrogel stiffness and oxygen tension affect cancer cell fate and endothelial sprouting. Biomaterials science. 2014 May;2(5):655–665.
Journal cover image

Published In

Biomaterials science

DOI

EISSN

2047-4849

ISSN

2047-4830

Publication Date

May 2014

Volume

2

Issue

5

Start / End Page

655 / 665

Related Subject Headings

  • 4003 Biomedical engineering
  • 3206 Medical biotechnology
  • 1004 Medical Biotechnology
  • 0601 Biochemistry and Cell Biology
  • 0304 Medicinal and Biomolecular Chemistry