Activation of Myeloid-Derived Suppressor Cells in Bone Marrow

Abstract

The overall goal of this research project was to investigate the mechanism of myeloid-derived suppressor cell (MDSC) activation within the bone marrow, in response to prostate cancer. The specific aims were designed to determine the effects of PTHrP-stimulated cytokine expression by osteoblasts on phosphorylation of Y418 Src family kinases in MDSs within the bone marrow, and to elucidate the effects of Src family kinases inhibition specifically in MDSCs on prostate tumor growth and angiogenesis. Experimental results from this study demonstrated that PTHrP drives an MDSC-mediated positive feedback loop to support prostate cancer growth. Furthermore, this study demonstrated that PTHrP increased tyrosine 418 residue phosphorylation levels in Src family kinases in MDSCs via osteoblast-derived IL-6 and VEGF-A, thereby upregulating MMP-9.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2013
Accession Number
ADA600504

Entities

People

  • Serk I. Park

Organizations

  • Vanderbilt University

Tags

DTIC Thesaurus Topics

  • Blood
  • Bone Diseases
  • Bone Marrow
  • Cardiovascular System
  • Cells
  • Gene Expression
  • Health Services
  • Lymphocytes
  • Macrophages
  • Mononuclear Phagocyte System
  • Osteoblasts
  • Peptides
  • Prostate Cancer
  • Proteins
  • Stem Cells
  • Tissues

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Immunology and Pathology
  • Oncology (Cancer Research).