Bone Marrow Microenvironmental Control of Prostate Cancer Skeletal Localization

Abstract

The purpose of this study is to analyze the role of prostate cancer derived PTHrP and its ability to impact the bone marrow microenvironment of the skeletal metastasis. During the first year of the project, PC-3 cell lines expressing luciferase and with altered PTHrP levels were generated and their activity verified in in vitro and in vivo assays. The PC-3 cell lines with lowered PTHrP levels (via shRNA knock down) developed smaller tumors. The PC-3 cell lines with lowered PTHrP levels showed a trend toward lowered hematopoietic progenitors in the bone marrow. Altering the bone marrow microenvironment with an agent that reduces HPCs (cyclophosphamide) increased tumor engraftment. Altering the bone marrow microenvironment with zoledronic acid (a proven anti-tumor therapy) increased HPCs. These studies have already provided early data that suggest there are key and controllable events that can be triggered in the bone marrow which are conducive to tumor growth.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2009
Accession Number
ADA514367

Entities

People

  • Laurie K. Mccauley

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Bioluminescence
  • Biomedical Research
  • Blood
  • Bone Marrow
  • Bone Marrow Cells
  • Bones
  • Cancer
  • Cell Line
  • Cells
  • Chemical Compounds
  • Cyclophosphamide
  • Hematopoietic Cells
  • Inoculation
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Stem Cells

Readers

  • Immunology and Pathology
  • Oncology (Cancer Research).