Hic-5's Regulatory Role in TGFB Signaling In Prostate Stroma

Abstract

In this study, we attempt to demonstrate that a reactive stroma maintains the ability to restrain cancer cell motility, but this inhibition is lost when local TGF production stimulates an increased production of stromal ROS that in turn inactivates the inhibitor. We show that in the absence of TGF , a myofibroblastic prostate stromal cell (WPMY 1) produces a motility inhibitory factor that limits motility in a highly aggressive PCa cell line (DU145). Additionally, we identified Cox 2 as the downstream target of TGF responsible for the loss of this inhibition, and we show that the inactivation of the inhibitor is via a ROS dependent mechanism generated as a byproduct of arachidonic acid conversion by Cox 2. These results suggest that local TGF production in the cancer milieu promotes increased metastatic potential by causing oxidative inactivation of a secreted stromal derived regulatory factor.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2011
Accession Number
ADA549000

Entities

People

  • Melanie Grubisha

Organizations

  • University of Pittsburgh

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Biomedical Research
  • Cancer
  • Cell Line
  • Cell Movement
  • Cells
  • Culture Media
  • Culture Techniques
  • Department Of Defense
  • Electronic Mail
  • Inhibition
  • Inhibitors
  • Neoplasms
  • Production
  • Prostate
  • Stromal Cells

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Prostate Cancer Biology.