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

Overview

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.

publication date

  • March 17, 2014

Research

keywords

  • Academic 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

  • 65

volume

  • 25

number

  • 3