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Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance
Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance
- Source :
- Cancer cell. 25(3)
- Publication Year :
- 2013
-
Abstract
- Summary 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.
- Subjects :
- JAG1
Cancer Research
Fibroblast Growth Factor 4
Genes, myc
Cell Cycle Proteins
Mice, Transgenic
Receptor, Macrophage Colony-Stimulating Factor
Biology
Receptor, IGF Type 1
03 medical and health sciences
Paracrine signalling
Mice
0302 clinical medicine
Downregulation and upregulation
medicine
Tumor Cells, Cultured
Animals
Humans
Neoplasm Invasiveness
Serrate-Jagged Proteins
Receptor, Fibroblast Growth Factor, Type 1
Receptor, Notch2
RNA, Small Interfering
B-cell lymphoma
030304 developmental biology
Insulin-like growth factor 1 receptor
Cell Proliferation
0303 health sciences
Cell growth
CD44
Calcium-Binding Proteins
Endothelial Cells
Membrane Proteins
Cell Biology
medicine.disease
Burkitt Lymphoma
Up-Regulation
Enzyme Activation
Hyaluronan Receptors
Oncology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer research
biology.protein
Intercellular Signaling Peptides and Proteins
RNA Interference
Signal transduction
Jagged-1 Protein
Signal Transduction
Subjects
Details
- ISSN :
- 18783686
- Volume :
- 25
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cancer cell
- Accession number :
- edsair.doi.dedup.....46732376a42b5c80c0d0373e81dd4ffc