The Dialogue of Metastasis-Uncovering Juxtacrine Genetic Cascades with a Toxoplasma Gondii Enzyme

Abstract

The purpose of this project is to develop and test a system that identifies in real time the effects of breast cancer cells on gene transcription by cells in their microenvironment. The accomplishment of this goal will identify messages induced in normal cells adjacent to cancer cells that support cancer cell growth and survival. In this Concept award project, we are testing whether breast cancer cells that make lysyl oxidase (a metastasis promoting enzyme) or have lysyl oxidase suppressed differ in their ability to turn on hospitable genes in bone marrow stromal cells. We have successfully tagged bone marrow stromal cells with a protozoal enzyme (uracil phosphoribosyl transferase) that enables us to measure ongoing stromal cell transcription when stroma is mixed with breast cancer cells. Real time transcription specific to the stromal cell compartment was able to be measured without disaggregating stromal and cancer cells, so that genetic signals arising from cell contact between stroma and cancer cells could be captured. A global assessment of stromal genes induced by high versus low metastatic cancer cells is planned. This project is likely to help guide the development of stromal-based therapeutics.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2008
Accession Number
ADA494955

Entities

People

  • Richard A. Steinman

Organizations

  • University of Pittsburgh

Tags

DTIC Thesaurus Topics

  • Bacterial Proteins
  • Biomedical Research
  • Bone Marrow
  • Bones
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cells
  • Communication Networks
  • Culture Techniques
  • Enzymes
  • Gene Expression
  • Metastasis
  • Neoplasms
  • Proteins
  • Stromal Cells

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Oncology (Cancer Research).
  • Systems Analysis and Design

Technology Areas

  • Biotechnology