Reactive Oxygen Species Produced by Prostate Cancer Cells Cause Castrate-Resistant Cell Growth by Inducing B-cell Lymphotoxin Release

Abstract

Lack of a clear understanding of the mechanism of prostate cancer (PCa) progression should help drugs to prevent castrate-resistant PCa (CRPCa) progression in early-stage recurrent PCa patients. It has long been established that androgen signaling induces ROS production specifically in PCa cells by inducing a polyamine oxidation pathway. It has been shown that inflammatory response due to PCa causes release of specific cytokines that leads to B-cell infiltration in the PCa microenvironment. The B-cells, in-turn, switch on lymphotoxin (LT and/or LT ) production that has been implicated in ADPCa progression to CRPCa. Androgen-induced H2O2 released by PCa cells in the tumor microenvironment causes inflammatory response, B-cell infiltration and LT release leading to PCa progression to CRPCa. We proposed to co-culture PCa and human B-cells, where nutrient and metabolites can be exchanged freely. We proposed to take a novel and innovative microfluidic approach for the co-culture to closely mimic the in vivo microenvironment to reduce/eliminate the dilution effects observed in Boyden chambers. We studied if ROS produced by PCa cells can induce LTs in B-cells that can help androgen-independent growth of ADPCa cells.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2013
Accession Number
ADA582385

Entities

People

  • Hirak S. Basu

Organizations

  • University of Wisconsin–Madison

Tags

DTIC Thesaurus Topics

  • Amines
  • Androgen Receptors
  • Androgens
  • Biomedical Research
  • Cell Line
  • Cells
  • Culture Media
  • Culture Techniques
  • Lymphotoxins
  • Materials
  • Medical Personnel
  • Molecules
  • Neoplasms
  • Oxidation
  • Oxidative Stress
  • Prostate Cancer
  • Small Molecules

Fields of Study

  • Medicine

Readers

  • Immunology
  • Oncology (Cancer Research).
  • Prostate Cancer Biology.