Journal
CANCER CELL
Volume 25, Issue 3, Pages 350-365Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2014.02.005
Keywords
-
Categories
Funding
- National Scientist Development Grant from the American Heart Association [12SDG1213004]
- New York Stem Cell Foundation
- Ansary Stem Cell Institute
- Howard Hughes Medical Institute
- New York State Department of Health [C024180, C026438, C026878, C028117]
- National Heart, Lung, and Blood Institute [R01HL097797, R01HL119872, RC2HL101846, HL119872, HL055748, R01 HL084619]
- National Institute of Diabetes and Digestive and Kidney Diseases [R01DK095039]
- National Cancer Institute [U54CA163167, CA159175, CA163167]
- Qatar National Priorities Research Foundation [NPRP08-663-3-140]
- Qatar Foundation BioMedical Research Program
- Angiocrine Bioscience, New York
- Leukemia & Lymphoma Society
- Empire State Stem Cell Board
Ask authors/readers for more resources
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 E mu-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available