Estrogen Mobilizes Circulating Bone Marrow Progenitor Cells to Promote Tumor Neovasculature: Lessions from Ischemic Model Provide a Novel Breast Cancer Target

Abstract

Breast cancer growth and metastases is dependent on neovasculature. The cells that actually trigger the formation of new blood vessels are poorly characterized but it has been hypothesized that some of the precursor blood vessel cells originate in the bone marrow and then home to tumor tissues. Although estrogen is a major stimulus, its role as a bone marrow originating endothelial cell mobilizing agent has not been demonstrated. We propose to test the proposition whether estrogen can mobilize circulating bone marrow derived progenitor endothelial cells (EPCs) to the implanted tumor using Green fluorescence protein, GFP, tagged EPCs. The objectives of the proposed study are two fold: A) Establishment of proposed Animal model using normal and OVX (ovariectomized) female BALB/c mice and examine if estrogen can indeed mobilize the EPCs for the generation of new blood vessels. B) To elucidate the contribution of E2-mobilized, BM-derived EPC in promoting neo-vascularization in implanted breast tumor. The mechanism of E2-induced mobilization of EPC from the bone marrow will open a new area of BrCa research and hence novel targets. Moreover, BM-EPCS could potentially serve as the "Trojan horse" to deliver bio-molecules that disrupt tumor vasculogenesis and/or induce targeted killing of tumor cells. Thus this novel basic concept has clinical potential.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2007
Accession Number
ADA479328

Entities

People

  • Raj K. Tiwari

Organizations

  • New York Medical College

Tags

DTIC Thesaurus Topics

  • Angiogenesis
  • Base Lines
  • Biomedical Research
  • Blood
  • Blood Vessels
  • Bone Marrow
  • Breast Cancer
  • Cells
  • Endothelial Cells
  • Estrogens
  • Fluorescence
  • Mammary Glands
  • Mobilization
  • Molecules
  • Neoplasms
  • Proteins
  • Stem Cells

Readers

  • Military Mobilization and Reserve Forces Studies.
  • Oncology (Cancer Research).