Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antigens, CD44
  • Cell Cycle Proteins
  • Cell Proliferation
  • Endothelial Cells
  • Enzyme Activation
  • Genes, myc
  • Humans
  • Jagged-1 Protein
  • Mice
  • Mice, Transgenic
  • Neoplasm Invasiveness
  • RNA Interference
  • RNA, Small Interfering
  • Receptor, IGF Type 1
  • Receptor, Macrophage Colony-Stimulating Factor
  • Serrate-Jagged Proteins
  • Signal Transduction
  • Tumor Cells, Cultured
  • Up-Regulation

MeSH Major

  • Burkitt Lymphoma
  • Calcium-Binding Proteins
  • Drug Resistance, Neoplasm
  • Fibroblast Growth Factor 4
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Notch2

abstract

  • Tumor endothelial cells (ECs) promote cancer progression in ways beyond their role as conduits supporting metabolism. However, it is unknown how vascular niche-derived paracrine factors, defined as angiocrine factors, provoke tumor aggressiveness. Here, we show that FGF4 produced by B cell lymphoma cells (LCs) through activating FGFR1 upregulates the Notch ligand Jagged1 (Jag1) on neighboring ECs. In turn, upregulation of Jag1 on ECs reciprocally induces Notch2-Hey1 in LCs. This crosstalk enforces aggressive CD44(+)IGF1R(+)CSF1R(+) LC phenotypes, including extranodal invasion and chemoresistance. Inducible EC-selective deletion of Fgfr1 or Jag1 in the Eμ-Myc lymphoma model or impairing Notch2 signaling in mouse and human LCs diminished lymphoma aggressiveness and prolonged mouse survival. Thus, targeting the angiocrine FGF4-FGFR1/Jag1-Notch2 loop inhibits LC aggressiveness and enhances chemosensitivity. Copyright © 2014 Elsevier Inc. All rights reserved.

publication date

  • March 17, 2014

has subject area

  • Animals
  • Antigens, CD44
  • Burkitt Lymphoma
  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Endothelial Cells
  • Enzyme Activation
  • Fibroblast Growth Factor 4
  • Genes, myc
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Neoplasm Invasiveness
  • RNA Interference
  • RNA, Small Interfering
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, IGF Type 1
  • Receptor, Macrophage Colony-Stimulating Factor
  • Receptor, Notch2
  • Serrate-Jagged Proteins
  • Signal Transduction
  • Tumor Cells, Cultured
  • Up-Regulation

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4017921

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2014.02.005

PubMed ID

  • 24651014

Additional Document Info

start page

  • 350

end page

  • 365

volume

  • 25

number

  • 3